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Wen J, Ding Z, Wei Z, Xia H, Zhang Y, Zhu X. NeuroPpred-SHE: An interpretable neuropeptides prediction model based on selected features from hand-crafted features and embeddings of T5 model. Comput Biol Med 2024; 181:109048. [PMID: 39182368 DOI: 10.1016/j.compbiomed.2024.109048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 08/13/2024] [Accepted: 08/18/2024] [Indexed: 08/27/2024]
Abstract
Neuropeptides are the most ubiquitous neurotransmitters in the immune system, regulating various biological processes. Neuropeptides play a significant role for the discovery of new drugs and targets for nervous system disorders. Traditional experimental methods for identifying neuropeptides are time-consuming and costly. Although several computational methods have been developed to predict the neuropeptides, the accuracy is still not satisfactory due to the representability of the extracted features. In this work, we propose an efficient and interpretable model, NeuroPpred-SHE, for predicting neuropeptides by selecting the optimal feature subset from both hand-crafted features and embeddings of a protein language model. Specially, we first employed a pre-trained T5 protein language model to extract embedding features and twelve other encoding methods to extract hand-crafted features from peptide sequences, respectively. Secondly, we fused both embedding features and hand-crafted features to enhance the feature representability. Thirdly, we utilized random forest (RF), Max-Relevance and Min-Redundancy (mRMR) and eXtreme Gradient Boosting (XGBoost) methods to select the optimal feature subset from the fused features. Finally, we employed five machine learning methods (GBDT, XGBoost, SVM, MLP, and LightGBM) to build the models. Our results show that the model based on GBDT achieves the best performance. Furthermore, our final model was compared with other state-of-the-art methods on an independent test set, the results indicate that our model achieves an AUROC of 97.8 % which is higher than all the other state-of-the-art predictors. Our model is available at: https://github.com/wenjean/NeuroPpred-SHE.
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Affiliation(s)
- Jian Wen
- School of Information and Artificial Intelligence, Anhui Agricultural University, Hefei, 230036, China
| | - Zhijie Ding
- School of Information and Artificial Intelligence, Anhui Agricultural University, Hefei, 230036, China
| | - Zhuoyu Wei
- School of Information and Artificial Intelligence, Anhui Agricultural University, Hefei, 230036, China
| | - Hongwei Xia
- School of Information and Artificial Intelligence, Anhui Agricultural University, Hefei, 230036, China
| | - Yong Zhang
- School of Information and Artificial Intelligence, Anhui Agricultural University, Hefei, 230036, China.
| | - Xiaolei Zhu
- School of Information and Artificial Intelligence, Anhui Agricultural University, Hefei, 230036, China.
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Karaagac Y, Özçelik AÖ. Nutritional status changes in the treatment of substance use disorder: Relationship with substance craving. Nutr Res 2024; 123:120-129. [PMID: 38335923 DOI: 10.1016/j.nutres.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 01/14/2024] [Accepted: 01/14/2024] [Indexed: 02/12/2024]
Abstract
Tailored nutrition counseling enhances the efficacy of routine treatment for substance (alcohol/drugs) use disorders (SUDs). For this purpose, it is important to understand the current nutritional status of addicts and the changes in their nutritional status during the treatment process. Furthermore, the consumption of sweets to manage substance cravings is common among people with SUDs, but the evidence for the effectiveness of this practice is limited and conflicting. We therefore hypothesized SUD treatment would be associated with increases in appetite, nutrient intake, and anthropometric measurements in addicts, and that these changes, including changes in sweet consumption, would not be associated with decreased substance craving. Data for this prospective observational study were collected from 38 adult male patients who completed 21 days of inpatient SUD treatment. During the treatment, the participants' levels of appetite (P < 1.0 × 10-4), the frequency of main meals (P < 1.0 × 10-4), intake of macro- and micronutrients (P < .05 for each), and anthropometric measurements (P ≤ 5.9 × 10-4), significantly increased. Furthermore, it was found that the patients had a significant increase in sweets craving (P < 1.0 × 10-4) and sweets consumption (P = 1.2 × 10-3) during treatment. However, there was no significant difference between the individuals whose craving decreased and those whose craving did not decrease at the end of the treatment (P > .05 for both). The findings suggest the need to offer dietary counseling to individuals undergoing inpatient SUD treatment, given the substantial changes in nutritional status, and that increased consumption of sweets is not an effective strategy to reduce substance craving.
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Affiliation(s)
- Yasemin Karaagac
- Izmir Katip Çelebi University, Faculty of Health Sciences, Department of Nutrition and Dietetic, Izmir, Turkey.
| | - Ayşe Özfer Özçelik
- Ankara University, Faculty of Health Sciences, Department of Nutrition and Dietetic, Ankara, Turkey
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3
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Sheng W, Sun R, Zhang R, Xu P, Wang Y, Xu H, Aa J, Wang G, Xie Y. Identification of Biomarkers for Methamphetamine Exposure Time Prediction in Mice Using Metabolomics and Machine Learning Approaches. Metabolites 2022; 12:metabo12121250. [PMID: 36557288 PMCID: PMC9780981 DOI: 10.3390/metabo12121250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/04/2022] [Accepted: 12/07/2022] [Indexed: 12/14/2022] Open
Abstract
Methamphetamine (METH) abuse has become a global public health and safety problem. More information is needed to identify the time of drug abuse. In this study, methamphetamine was administered to male C57BL/6J mice with increasing doses from 5 to 30 mg kg-1 (once a day, i.p.) for 20 days. Serum and urine samples were collected for metabolomics studies using gas chromatography-mass spectrometry (GC-MS). Six machine learning models were used to infer the time of drug abuse and the best model was selected to predict administration time preliminarily. The metabolic changes caused by methamphetamine were explored. As results, the metabolic patterns of methamphetamine exposure mice were quite different from the control group and changed over time. Specifically, serum metabolomics showed enhanced amino acid metabolism and increased fatty acid consumption, while urine metabolomics showed slowed metabolism of the tricarboxylic acid (TCA) cycle, increased organic acid excretion, and abnormal purine metabolism. Phenylalanine in serum and glutamine in urine increased, while palmitic acid, 5-HT, and monopalmitin in serum and gamma-aminobutyric acid in urine decreased significantly. Among the six machine learning models, the random forest model was the best to predict the exposure time (serum: MAE = 1.482, RMSE = 1.69, R squared = 0.981; urine: MAE = 2.369, RMSE = 1.926, R squared = 0.946). The potential biomarker set containing four metabolites in the serum (palmitic acid, 5-hydroxytryptamine, monopalmitin, and phenylalanine) facilitated the identification of methamphetamine exposure. The random forest model helped predict the methamphetamine exposure time based on these potential biomarkers.
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Affiliation(s)
- Wei Sheng
- China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing 210000, China
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Runbin Sun
- China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing 210000, China
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Ran Zhang
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Peng Xu
- China National Narcotics Control Commission—China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, China Pharmaceutical University, Nanjing 210009, China
| | - Youmei Wang
- China National Narcotics Control Commission—China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, China Pharmaceutical University, Nanjing 210009, China
| | - Hui Xu
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Jiye Aa
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
| | - Guangji Wang
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
- Correspondence: (G.W.); (Y.X.)
| | - Yuan Xie
- Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
- Correspondence: (G.W.); (Y.X.)
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Shang Q, Wang J, Xi Z, Gao B, Qian H, An R, Shao G, Liu H, Li T, Liu X. Mechanisms underlying microRNA-222-3p modulation of methamphetamine-induced conditioned place preference in the nucleus accumbens in mice. Psychopharmacology (Berl) 2022; 239:2997-3008. [PMID: 35881147 DOI: 10.1007/s00213-022-06183-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 06/20/2022] [Indexed: 11/24/2022]
Abstract
RATIONALE MicroRNA (miRNA) control of post-transcription gene expression in the nucleus accumbens (NAc) has been implicated in methamphetamine (METH) dependence. Conditioned place preference (CPP) is a classical animal procedure that reflects the rewarding effects of addictive drugs. miR-222-3p has been reported to play a key role in various neurological diseases and is strongly associated with alcohol dependence. Nevertheless, the role of miR-222-3p in METH dependence remains unclear. OBJECTIVE To explore the molecular mechanisms underlying the role of miR-222-3p in the NAc in METH-induced CPP. METHODS miR-222-3p expression in the NAc of METH-induced CPP mice was detected by quantitative real-time (qPCR). Following adeno-associated virus (AAV)-mediated overexpression or knockdown of miR-222-3p in the NAc, mice were subjected to CPP to investigate the effects of miR-222-3p on METH-induced CPP. Target genes of mir-222-3p were predicted using bioinformatics analysis. Candidate target genes for METH-induced CPP were validated by qPCR. RESULTS miR-222-3p expression in the NAc was decreased in CPP mice. Overexpression of miR-222-3p in the NAc blunted METH-induced CPP. Ppp3r1, Cdkn1c, Fmr1, and PPARGC1A were identified as target gene transcripts potentially mediating the effects of miR-222-3p on METH-induced CPP. CONCLUSION Our results highlight miR-222-3p as a key epigenetic regulator in METH-induced CPP and suggest a potential role for miR-222-3p in the regulation of METH-induced reward-related changes in the brain.
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Affiliation(s)
- Qing Shang
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Jing Wang
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Zhijia Xi
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Baoyao Gao
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Hongyan Qian
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Ran An
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Gaojie Shao
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Hua Liu
- Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing, People's Republic of China
| | - Tao Li
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China. .,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China.
| | - Xinshe Liu
- Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China. .,College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China.
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5
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Chen S, Li Q, Zhao J, Bin Y, Zheng C. NeuroPred-CLQ: incorporating deep temporal convolutional networks and multi-head attention mechanism to predict neuropeptides. Brief Bioinform 2022; 23:6672901. [DOI: 10.1093/bib/bbac319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/27/2022] [Accepted: 07/14/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Neuropeptides (NPs) are a particular class of informative substances in the immune system and physiological regulation. They play a crucial role in regulating physiological functions in various biological growth and developmental stages. In addition, NPs are crucial for developing new drugs for the treatment of neurological diseases. With the development of molecular biology techniques, some data-driven tools have emerged to predict NPs. However, it is necessary to improve the predictive performance of these tools for NPs. In this study, we developed a deep learning model (NeuroPred-CLQ) based on the temporal convolutional network (TCN) and multi-head attention mechanism to identify NPs effectively and translate the internal relationships of peptide sequences into numerical features by the Word2vec algorithm. The experimental results show that NeuroPred-CLQ learns data information effectively, achieving 93.6% accuracy and 98.8% AUC on the independent test set. The model has better performance in identifying NPs than the state-of-the-art predictors. Visualization of features using t-distribution random neighbor embedding shows that the NeuroPred-CLQ can clearly distinguish the positive NPs from the negative ones. We believe the NeuroPred-CLQ can facilitate drug development and clinical trial studies to treat neurological disorders.
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Affiliation(s)
- Shouzhi Chen
- School of Mathematics and System Science, Xinjiang University , Urumqi, China
| | - Qing Li
- School of Mathematics and System Science, Xinjiang University , Urumqi, China
| | - Jianping Zhao
- School of Mathematics and System Science, Xinjiang University , Urumqi, China
| | - Yannan Bin
- School of Computer Science and Technology, Anhui University , Hefei, China
| | - Chunhou Zheng
- School of Mathematics and System Science, Xinjiang University , Urumqi, China
- School of Computer Science and Technology, Anhui University , Hefei, China
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6
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Méndez-Couz M, González-Pardo H, Arias JL, Conejo NM. Hippocampal neuropeptide Y 2 receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism. Neurobiol Learn Mem 2021; 187:107561. [PMID: 34838984 DOI: 10.1016/j.nlm.2021.107561] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 11/17/2021] [Accepted: 11/19/2021] [Indexed: 10/19/2022]
Abstract
INTRODUCTION The neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y2 receptor (Y2R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y2R remain unclear. METHODS Here, we examined the involvement of the hippocampal NPY Y2R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions. RESULTS The acute blockade of NPY Y2R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies. CONCLUSIONS These findings suggest that the NPY hippocampal system, through its Y2R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y2R modulation of long-term potentiation and long-term depression.
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Affiliation(s)
- Marta Méndez-Couz
- Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Pl. Feijoo s/n, 33003 Oviedo, Spain; Dept. Neurophysiology. Medical Faculty, Ruhr-University Bochum. Universitätsstraße, 150. Building MA 01/551, 44780 Bochum, Germany.
| | - Héctor González-Pardo
- Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Pl. Feijoo s/n, 33003 Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Jorge L Arias
- Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Pl. Feijoo s/n, 33003 Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Nélida M Conejo
- Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Pl. Feijoo s/n, 33003 Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
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Hime GR, Stonehouse SLA, Pang TY. Alternative models for transgenerational epigenetic inheritance: Molecular psychiatry beyond mice and man. World J Psychiatry 2021; 11:711-735. [PMID: 34733638 PMCID: PMC8546770 DOI: 10.5498/wjp.v11.i10.711] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/19/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
Mental illness remains the greatest chronic health burden globally with few in-roads having been made despite significant advances in genomic knowledge in recent decades. The field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations, and that has to be supported by a continuous growth in knowledge. The majority of neuropsychiatric symptoms reflect complex gene-environment interactions, with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of symptoms. It has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stress-related behavioural phenotypes in both paternal and maternal lineages, providing further supporting evidence for heritability in humans. However, unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric conditions. While rodents will remain the dominant model system for preclinical studies (especially for addressing complex behavioural phenotypes), there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate models. Here, we will discuss the utility and advantages of two alternative model organisms-Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.
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Affiliation(s)
- Gary R Hime
- Department of Anatomy and Physiology, The University of Melbourne, Parkville 3010, VIC, Australia
| | - Sophie LA Stonehouse
- Mental Health Theme, The Florey Institute of Neuroscience and Mental Health, Parkville 3052, VIC, Australia
| | - Terence Y Pang
- Department of Anatomy and Physiology, The University of Melbourne, Parkville 3010, VIC, Australia
- Mental Health Theme, The Florey Institute of Neuroscience and Mental Health, Parkville 3052, VIC, Australia
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Zheng YL, Wang WD, Li MM, Lin S, Lin HL. Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis. Front Cardiovasc Med 2021; 8:630968. [PMID: 33708805 PMCID: PMC7940677 DOI: 10.3389/fcvm.2021.630968] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 02/03/2021] [Indexed: 12/18/2022] Open
Abstract
Cardiovascular disease is the leading cause of death worldwide. Endothelial dysfunction of the arterial vasculature plays a pivotal role in cardiovascular pathogenesis. Nicotine-induced endothelial dysfunction substantially contributes to the development of arteriosclerotic cardiovascular disease. Nicotine promotes oxidative inflammation, thrombosis, pathological angiogenesis, and vasoconstriction, and induces insulin resistance. However, the exact mechanism through which nicotine induces endothelial dysfunction remains unclear. Neuropeptide Y (NPY) is widely distributed in the central nervous system and peripheral tissues, and it participates in the pathogenesis of atherosclerosis by regulating vasoconstriction, energy metabolism, local plaque inflammatory response, activation and aggregation of platelets, and stress and anxiety-related emotion. Nicotine can increase the expression of NPY, suggesting that NPY is involved in nicotine-induced endothelial dysfunction. Herein, we present an updated review of the possible mechanisms of nicotine-induced atherosclerosis, with a focus on endothelial cell dysfunction associated with nicotine and NPY.
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Affiliation(s)
- Yan-Li Zheng
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Wan-da Wang
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Mei-Mei Li
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Shu Lin
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.,Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.,Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Hui-Li Lin
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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Chen B, Yadav M, Mulkalwar M, Saikrishna L, Verma H, Ye W, Bhaskar LVKS. Meta-Analysis on the Association of Neuropeptide Y rs16139 Variant With the Risk of Alcoholism. Front Psychiatry 2021; 12:737440. [PMID: 34777047 PMCID: PMC8583313 DOI: 10.3389/fpsyt.2021.737440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 10/04/2021] [Indexed: 11/13/2022] Open
Abstract
Introduction: The neuropeptide-Y (NPY) is involved in the development of alcoholism through NPY receptors. A T>C mutation causes substitution of leucine to proline at codon 7 (L7P; rs16139) in the signal peptide of neuropeptide Y is known to cause a 42% increase in plasma NPY levels. Studies that analyzed the association between NPY rs16139 and alcoholism risk did not demonstrate conclusive evidence for this relationship. The present study aims to evaluate the association between NPY gene rs16139 variant and alcohol dependence. Method: An electronic search of databases including PubMed and Google Scholar was performed to retrieve studies investigating the association between NPY rs16139 and alcoholism. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in allelic and dominant genetic models. Sensitivity analyses and publication bias were assessed in our meta-analysis. The meta-analysis was conducted using the MetaGenyo web tool. Result: Significant heterogeneity was observed across studies (p < 0.001). Our results have shown that there is no significant association between NPY rs16139 variant and the risk of alcoholism in allelic (OR = 0.98, 95% CI 0.70-1.38, p = 0.921) and dominant models (OR = 0.98, 95% CI 0.69-1.40, p = 0.919). Begg's funnel plot and Egger's test have not shown publication bias (p = 0.332). Conclusion: To the best of our knowledge, this is the first meta-analysis that evaluates the relationship between the NPY rs16139 polymorphism and the risk of alcoholism. Our large-scale meta-analysis suggests that NPY rs16139 polymorphism is not associated with alcoholism. However, further studies are needed to increase our understanding of the relationship between NPY variants in alcoholism.
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Affiliation(s)
- Biqing Chen
- Department of Sports Operation and Management, Jinhua Polytechnic, Jinhua, China
| | - Manish Yadav
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India
| | - Madhubala Mulkalwar
- Department of Pathology, Shri Shankaracharya Institute of Medical Sciences (SSIMS), Bhilai, India
| | | | - Henu Verma
- Department of Immunopathology, Institute of Lungs Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum, Munich, Germany
| | - Weibing Ye
- Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, China
| | - L V K S Bhaskar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India
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10
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Ventura F, Muga M, Coelho-Santos V, Fontes-Ribeiro CA, Leitão RA, Silva AP. Protective effect of neuropeptide Y2 receptor activation against methamphetamine-induced brain endothelial cell alterations. Toxicol Lett 2020; 334:53-59. [PMID: 32956829 DOI: 10.1016/j.toxlet.2020.09.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 09/09/2020] [Accepted: 09/15/2020] [Indexed: 12/20/2022]
Abstract
Methamphetamine (METH) consumption is a health problem that leads to neurological and psychiatric disturbances. The cellular alterations behind these conditions have been extensively investigated and it is now well-established that METH causes cerebrovascular alterations being a key feature in drug-induced neuropathology. Although promising advances in understanding the blood-brain barrier (BBB) alterations induced by METH, there is still no available approach to counteract or diminish such effects. Interestingly, several studies show that neuropeptide Y (NPY) has an important protective role against METH-induced neuronal and glial toxicity, as well as behavioral deficits. Despite these beneficial effects of the NPY system, nothing is known about its role in brain endothelial cells under conditions of METH exposure. Thus, our aim was to unravel the effect of NPY and its receptors against METH-induced endothelial cell dysfunction. For that, we used a human brain microvascular endothelial cell line (hCMEC/D3) and our results demonstrate that endothelial cells express both NPY Y1 (Y1R) and Y2 (Y2R) receptors, but only Y2R is upregulated after METH exposure. Moreover, this drug of abuse induced endothelial cell death and elicited the production of reactive oxygen species (ROS) by these cells, which were prevented by the activation of Y2R. Additional, cell death and oxidative stress triggered by METH were dependent on the concentration of the drug. In sum, with the present study we identified for the first time the NPY system, and particularly the Y2R subtype, as a promising target to protect against METH-induced neurovascular dysfunction.
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Affiliation(s)
- Fabiana Ventura
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal; Coimbra Hospital and University Centre, Coimbra, Portugal
| | - Mariana Muga
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
| | - Vanessa Coelho-Santos
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
| | - Carlos A Fontes-Ribeiro
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
| | - Ricardo A Leitão
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
| | - Ana Paula Silva
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
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11
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Bin Y, Zhang W, Tang W, Dai R, Li M, Zhu Q, Xia J. Prediction of Neuropeptides from Sequence Information Using Ensemble Classifier and Hybrid Features. J Proteome Res 2020; 19:3732-3740. [DOI: 10.1021/acs.jproteome.0c00276] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Yannan Bin
- Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
- School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China
| | - Wei Zhang
- Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
| | - Wending Tang
- Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
| | - Ruyu Dai
- Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
| | - Menglu Li
- School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China
| | - Qizhi Zhu
- Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
| | - Junfeng Xia
- Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
- School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China
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12
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Kang W, Lu D, Yang X, Ma W, Chen X, Chen K, Xu X, Zhou X, Zhou L, Feng X. Sevoflurane Induces Hippocampal Neuronal Apoptosis by Altering the Level of Neuropeptide Y in Neonatal Rats. Neurochem Res 2020; 45:1986-1996. [PMID: 32378074 DOI: 10.1007/s11064-020-03028-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 04/03/2020] [Accepted: 04/07/2020] [Indexed: 12/31/2022]
Abstract
Numerous studies have shown that the inhaled general anesthetic sevoflurane imposes toxicity on the central nervous system during the developmental period but the underlying mechanisms remain unclear. Neuropeptide Y (NPY) was reported to have important neuroprotective effects, which can attenuate neuronal loss under pathological conditions. However, the effects of NPY on sevoflurane-induced hippocampal neuronal apoptosis have not been investigated. In this study, postnatal day 7 (PND7) Sprague-Dawley rats and primary cultured cells separated from hippocampi were exposed to sevoflurane (2.4% for 4 h) and the NPY expression levels after treatment were analyzed. Furthermore, neuronal apoptosis assay was conducted via immunofluorescence staining of cleaved caspase-3 and flow cytometry after exogenous NPY administration to PND7 rats as well as cultured hippocampal neurons to elucidate the role of NPY in sevoflurane-induced neurotoxicity. Our results showed the level of NPY gradually decreased within 24 h after sevoflurane exposure in both the hippocampus of PND7 rats and cultured hippocampal neurons, but not in cultured astrocytes. In the exogenous NPY pretreatment study, the proportion of cleaved caspase-3 positive cells in the CA1 region of the hippocampus was increased significantly at 24 h after sevoflurane treatment, while NPY pretreatment could reduce it. Similarly, NPY could also reverse the apoptogenic effect of sevoflurane on cultured neurons. Herein, our results showed that sevoflurane caused a significant decrease in NPY expression, whereas exogenous NPY supplementation could reduce sevoflurane-induced hippocampal neuronal apoptosis both in vivo and in vitro.
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Affiliation(s)
- Wenbin Kang
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Dihan Lu
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Xiaoyu Yang
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Wudi Ma
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Xi Chen
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Keyu Chen
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Xuanxian Xu
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Xue Zhou
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China.
| | - Lihua Zhou
- Department of Anatomy, School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China.
| | - Xia Feng
- Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China.
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Abstract
Despite decades of research, few medications have gained Food and Drug Administration (FDA) approval for the management of substance abuse disorder. The paucity of successful medications can be attributed, in part, to the lack of clearly identified neurobiological targets for addressing the core pathology of addictive behavior. Commonalities in the behavioral and brain processes involved in the rewarding effects of drugs and foods has prompted the evaluation of candidate medications that target neural pathways involved in both drug and eating disorders. Here, pharmacological strategies for the development of novel medications for drug addiction are presented in the context of potential overlapping neurobiological targets identified for eating disorders (e.g., obesity, overeating, binge-eating) and substance abuse. Mechanisms discussed in this chapter include modulators of the gut-brain axis (e.g., leptin, ghrelin, cholecystokinin, cocaine- and amphetamine-regulated transcript, and pancreatic peptides) and neurotransmitter systems (e.g., opioids, cannabinoids, dopamine, serotonin, and acetylcholine).
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Roviš D, Vasiljev V, Jenko-Pražnikar Z, Petelin A, Drevenšek G, Peruč D, Černelič-Bizjak M. Mental health and drug use severity: the role of substance P, neuropeptide Y, self-reported childhood history of trauma, parental bonding and current resiliency. J Ment Health 2019; 30:88-96. [PMID: 31347421 DOI: 10.1080/09638237.2019.1644492] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Many risk factors lead to opioid use and drug-related problems. One of the challenges to understand behavioural factors, drug problems and psychopathology is to identify biological markers that are suitable for research on broad substance abuse and dependence involving human participants. AIMS The study has examined the relationships between the self-reported childhood history of trauma, parental bonding, psychopathology, impulsivity, current resiliency, two neuropeptides, possible markers of behaviour and emotion regulation, and severity of drug-related problems. METHODS One hundred and sixty-seven individuals with a history of opioid use completed questionnaires. Serum neuropeptide Y (NPY) and substance P (SP) levels were analysed. Moderating and mediating relationships between variables were examined using structural equation modelling (SEM). RESULTS Antisocial features, depression, impulsivity, SP, NPY, emotional neglect and resilience are associated with severity of drug-related problems. SP is associated with antisocial personality traits. CONCLUSIONS The novelty of this study is the proposed possible link between biochemical markers, antisocial features and behavioural and emotional regulation. Serum NPY and SP levels have a potential to be used as a biomarker in opioid users before and in the treatment process to account for interactions between biological vulnerabilities and childhood risk factors in predicting behavioural adjustment and more severe drug-related problems.
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Affiliation(s)
- Darko Roviš
- Department of Social Medicine and Epidemiology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Vanja Vasiljev
- Department of Social Medicine and Epidemiology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Zala Jenko-Pražnikar
- Department of Nutritional Counselling - Dietetics, Faculty of Health Sciences, University of Primorska, Izola, Slovenia
| | - Ana Petelin
- Department of Nutritional Counselling - Dietetics, Faculty of Health Sciences, University of Primorska, Izola, Slovenia
| | - Gorazd Drevenšek
- Department of Psychology, Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Koper, Slovenia
| | - Dolores Peruč
- Department of Social Medicine and Epidemiology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Maša Černelič-Bizjak
- Department of Nutritional Counselling - Dietetics, Faculty of Health Sciences, University of Primorska, Izola, Slovenia
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Bozler J, Kacsoh BZ, Bosco G. Transgeneratonal inheritance of ethanol preference is caused by maternal NPF repression. eLife 2019; 8:45391. [PMID: 31287057 PMCID: PMC6615861 DOI: 10.7554/elife.45391] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 05/22/2019] [Indexed: 12/17/2022] Open
Abstract
Rapid or even anticipatory adaptation to environmental conditions can provide a decisive fitness advantage to an organism. The memory of recurring conditions could also benefit future generations; however, neuronally-encoded behavior isn’t thought to be inherited across generations. We tested the possibility that environmentally triggered modifications could allow ‘memory’ of parental experiences to be inherited. In Drosophila melanogaster, exposure to predatory wasps leads to inheritance of a predisposition for ethanol-rich food for five generations. Inhibition of Neuropeptide-F (NPF) activates germline caspases required for transgenerational ethanol preference. Further, inheritance of low NPF expression in specific regions of F1 brains is required for the transmission of this food preference: a maternally derived NPF locus is necessary for this phenomenon, implicating a maternal epigenetic mechanism of NPF-repression. Given the conserved signaling functions of NPF and its mammalian NPY homolog in drug and alcohol disorders, these observations raise the intriguing possibility of NPY-related transgenerational effects in humans.
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Affiliation(s)
- Julianna Bozler
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
| | - Balint Z Kacsoh
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
| | - Giovanni Bosco
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
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16
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Ruisoto P, Contador I. The role of stress in drug addiction. An integrative review. Physiol Behav 2019; 202:62-68. [PMID: 30711532 DOI: 10.1016/j.physbeh.2019.01.022] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 01/30/2019] [Accepted: 01/30/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND The high prevalence and burden to society of drug abuse and addiction is undisputed. However, its conceptualisation as a brain disease is controversial, and available interventions insufficient. Research on the role of stress in drug addiction may bridge positions and develop more effective interventions. AIM The aim of this paper is to integrate the most influential literature to date on the role of stress in drug addiction. METHODS A literature search was conducted of the core collections of Web of Science and Semantic Scholar on the topic of stress and addiction from a neurobiological perspective in humans. The most frequently cited articles and related references published in the last decade were finally redrafted into a narrative review based on 130 full-text articles. RESULTS AND DISCUSSION First, a brief overview of the neurobiology of stress and drug addiction is provided. Then, the role of stress in drug addiction is described. Stress is conceptualised as a major source of allostatic load, which result in progressive long-term changes in the brain, leading to a drug-prone state characterized by craving and increased risk of relapse. The effects of stress on drug addiction are mainly mediated by the action of corticotropin-releasing factor and other stress hormones, which weaken the hippocampus and prefrontal cortex and strengthen the amygdala, leading to a negative emotional state, craving and lack of executive control, increasing the risk of relapse. Both, drugs and stress result in an allostatic overload responsible for neuroadaptations involved in most of the key features of addiction: reward anticipation/craving, negative affect, and impaired executive functions, involved in three stages of addiction and relapse. CONCLUSION This review elucidates the crucial role of stress in drug addiction and highlights the need to incorporate the social context where brain-behaviour relationships unfold into the current model of addition.
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Affiliation(s)
- Pablo Ruisoto
- Department of Psychobiology, Methodology and Behavioral Sciences, Faculty of Psychology, University of Salamanca, Spain.
| | - Israel Contador
- Department of Psychobiology, Methodology and Behavioral Sciences, Faculty of Psychology, University of Salamanca, Spain
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17
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Wiss DA. The Role of Nutrition in Addiction Recovery. THE ASSESSMENT AND TREATMENT OF ADDICTION 2019:21-42. [DOI: 10.1016/b978-0-323-54856-4.00002-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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From Synapse to Function: A Perspective on the Role of Neuroproteomics in Elucidating Mechanisms of Drug Addiction. Proteomes 2018; 6:proteomes6040050. [PMID: 30544849 PMCID: PMC6315754 DOI: 10.3390/proteomes6040050] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 12/05/2018] [Accepted: 12/07/2018] [Indexed: 12/18/2022] Open
Abstract
Drug addiction is a complex disorder driven by dysregulation in molecular signaling across several different brain regions. Limited therapeutic options currently exist for treating drug addiction and related psychiatric disorders in clinical populations, largely due to our incomplete understanding of the molecular pathways that influence addiction pathology. Recent work provides strong evidence that addiction-related behaviors emerge from the convergence of many subtle changes in molecular signaling networks that include neuropeptides (neuropeptidome), protein-protein interactions (interactome) and post-translational modifications such as protein phosphorylation (phosphoproteome). Advancements in mass spectrometry methodology are well positioned to identify these novel molecular underpinnings of addiction and further translate these findings into druggable targets for therapeutic development. In this review, we provide a general perspective of the utility of novel mass spectrometry-based approaches for addressing critical questions in addiction neuroscience, highlighting recent innovative studies that exemplify how functional assessments of the neuroproteome can provide insight into the mechanisms of drug addiction.
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Womersley JS, Townsend DM, Kalivas PW, Uys JD. Targeting redox regulation to treat substance use disorder using N‐acetylcysteine. Eur J Neurosci 2018; 50:2538-2551. [PMID: 30144182 DOI: 10.1111/ejn.14130] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 06/28/2018] [Accepted: 07/25/2018] [Indexed: 12/17/2022]
Abstract
Substance use disorder (SUD) is a chronic relapsing disorder characterized by transitioning from acute drug reward to compulsive drug use. Despite the heavy personal and societal burden of SUDs, current treatments are limited and unsatisfactory. For this reason, a deeper understanding of the mechanisms underlying addiction is required. Altered redox status, primarily due to drug-induced increases in dopamine metabolism, is a unifying feature of abused substances. In recent years, knowledge of the effects of oxidative stress in the nervous system has evolved from strictly neurotoxic to include a more nuanced role in redox-sensitive signaling. More specifically, S-glutathionylation, a redox-sensitive post-translational modification, has been suggested to influence the response to drugs of abuse. In this review we will examine the evidence for redox-mediating drugs as therapeutic tools focusing on N-acetylcysteine as a treatment for cocaine addiction. We will conclude by suggesting future research directions that may further advance this field.
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Affiliation(s)
- Jacqueline S Womersley
- Department of Cellular and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 409 Drug Discovery Building, 70 President Street, Charleston, SC, 29425, USA
| | - Danyelle M Townsend
- Department of Drug Discover and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Peter W Kalivas
- Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA
| | - Joachim D Uys
- Department of Cellular and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 409 Drug Discovery Building, 70 President Street, Charleston, SC, 29425, USA
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20
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Jeynes KD, Gibson EL. The importance of nutrition in aiding recovery from substance use disorders: A review. Drug Alcohol Depend 2017; 179:229-239. [PMID: 28806640 DOI: 10.1016/j.drugalcdep.2017.07.006] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 07/06/2017] [Accepted: 07/07/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND Nutrition is a prerequisite for health; yet, there is no special nutritional assessment or guidance for drug and alcohol dependent individuals, despite the fact that their food consumption is often very limited, risking malnutrition. Further, the premise is examined that malnutrition may promote drug seeking and impede recovery from substance use disorders (SUD). METHOD A narrative review addressed the relationship between substance use disorders and nutrition, including evidence for malnutrition, as well as their impact on metabolism and appetite regulation. The implications of the biopsychology of addiction and appetite for understanding the role of nutrition in SUD were also considered. RESULTS The literature overwhelmingly finds that subjects with alcohol use disorder (AUD) and drug use disorder (DUD) typically suffer from nutrient deficiencies. These nutrient deficiencies may be complicit in the alcoholic myopathy, osteopenia and osteoporosis, and mood disorders including anxiety and depression, observed in AUD and DUD. These same individuals have also been found to have altered body composition and altered hormonal metabolic regulators. Additionally, brain processes fundamental for survival are stimulated both by food, particularly sweet foods, and by substances of abuse, with evidence supporting confusion (addiction transfer) when recovering from SUD between cravings for a substance and craving for food. CONCLUSION Poor nutritional status in AUD and DUD severely impacts their physical and psychological health, which may impede their ability to resist substances of abuse and recover their health. This review contributes to a better understanding of interventions that could best support individuals with substance use disorders.
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Affiliation(s)
- Kendall D Jeynes
- Department of Life Sciences, Whitelands College, University of Roehampton, London SW15 4JD, UK
| | - E Leigh Gibson
- Department of Psychology, Whitelands College, University of Roehampton, Holybourne Avenue, London SW15 4JD, UK.
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21
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Ueno M, Yamada K, Ichitani Y. The relationship between fear extinction and resilience to drug-dependence in rats. Neurosci Res 2017; 121:37-42. [DOI: 10.1016/j.neures.2017.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 02/28/2017] [Accepted: 03/09/2017] [Indexed: 12/15/2022]
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22
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Chang X, Liu Y, Hahn CG, Gur RE, Sleiman PMA, Hakonarson H. RNA-seq analysis of amygdala tissue reveals characteristic expression profiles in schizophrenia. Transl Psychiatry 2017; 7:e1203. [PMID: 28809853 PMCID: PMC5611723 DOI: 10.1038/tp.2017.154] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 05/02/2017] [Accepted: 05/30/2017] [Indexed: 12/15/2022] Open
Abstract
The amygdala brain region has been implicated in the pathophysiology of schizophrenia through emotion processing. However, transcriptome messages in the amygdala of schizophrenia patients have not been well studied. We used RNA sequencing to investigate gene-expression profiling in the amygdala tissues, and identified 569 upregulated and 192 downregulated genes from 22 schizophrenia patients and 24 non-psychiatric controls. Gene functional enrichment analysis demonstrated that the downregulated genes were enriched in pathways such as 'synaptic transmission' and 'behavior', whereas the upregulated genes were significantly over-represented in gene ontology pathways such as 'immune response' and 'blood vessel development'. Co-expression-based gene network analysis identified seven modules including four modules significantly associated with 'synaptic transmission', 'blood vessel development' or 'immune responses'. Taken together, our study provides novel insights into the molecular mechanism of schizophrenia, suggesting that precision-tailored therapeutic approaches aimed at normalizing the expression/function of specific gene networks could be a promising option in schizophrenia.
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Affiliation(s)
- X Chang
- Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Y Liu
- Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - C-G Hahn
- Neuropsychiatric Signaling Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - R E Gur
- Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - P M A Sleiman
- Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA,Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - H Hakonarson
- Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA,Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA,Leonard Madlyn Abramson Research Center, 3615 Civic Center Boulevard, Room 1216E, Philadelphia, PA 19104-4318, USA. E-mail:
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23
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Effects of drugs of abuse on the central neuropeptide Y system. Addict Biol 2017; 22:882. [PMID: 28398010 DOI: 10.1111/adb.12518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Thorsell A, Mathé AA. Neuropeptide Y in Alcohol Addiction and Affective Disorders. Front Endocrinol (Lausanne) 2017; 8:178. [PMID: 28824541 PMCID: PMC5534438 DOI: 10.3389/fendo.2017.00178] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2016] [Accepted: 07/07/2017] [Indexed: 12/31/2022] Open
Abstract
Neuropeptide Y (NPY), a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS), as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide's regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor subtypes, may be attractive targets for treatment development for affective disorders, as well as for alcohol use disorders.
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Affiliation(s)
- Annika Thorsell
- Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
- *Correspondence: Annika Thorsell,
| | - Aleksander A. Mathé
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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Schmeltzer SN, Herman JP, Sah R. Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update. Exp Neurol 2016; 284:196-210. [PMID: 27377319 PMCID: PMC8375392 DOI: 10.1016/j.expneurol.2016.06.020] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 06/15/2016] [Accepted: 06/20/2016] [Indexed: 12/12/2022]
Abstract
Posttraumatic stress disorder (PTSD) is a trauma-evoked syndrome, with variable prevalence within the human population due to individual differences in coping and resiliency. In this review, we discuss evidence supporting the relevance of neuropeptide Y (NPY), a stress regulatory transmitter in PTSD. We consolidate findings from preclinical, clinical, and translational studies of NPY that are of relevance to PTSD with an attempt to provide a current update of this area of research. NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors. Studies in rodents demonstrate a role for NPY in stress responses, anxiety, fear, and autonomic regulation, all relevant to PTSD symptomology. Genetic studies support an association of NPY polymorphisms with stress coping and affect. Importantly, cerebrospinal fluid (CSF) measurements in combat veterans provide direct evidence of NPY association with PTSD diagnosis and symptomology. In addition, NPY involvement in pain, depression, addiction, and metabolism may be relevant to comorbidities associated with PTSD. Collectively, the literature supports the relevance of NPY to PTSD pathophysiology, although knowledge gaps remain. The NPY system is an attractive target in terms of understanding the physiological basis of PTSD as well as treatment of the disorder.
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Affiliation(s)
- Sarah N Schmeltzer
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45237, United States
| | - James P Herman
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45237, United States
| | - Renu Sah
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45237, United States; VA Medical Center, Cincinnati, OH, 45220, United States.
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