Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Aug 19, 2023; 13(8): 511-523
Published online Aug 19, 2023. doi: 10.5498/wjp.v13.i8.511
Dexmedetomidine mediates the mechanism of action of ferroptosis in mice with Alzheimer’s disease by regulating the mTOR-TFR1 pathway
Li Qiao, Gang Li, Hong-Xun Yuan
Li Qiao, Gang Li, Hong-Xun Yuan, Intensive Care Unit, Peking University International Hospital, Beijing 102206, China
Author contributions: Qiao L and Yuan HX conceived the study design and the content concept; Li G and Yuan HX performed data collection, extraction and analysis, interpreted and reviewed the data and drafts; Qiao L, Li G, and Yuan HX reviewed the final draft. Li G and Yuan HX are co-corresponding authors with equal contribution to the article.
Supported by Peking University International Hospital Foundation for Scientific Research, No. YN2022QN11.
Institutional animal care and use committee statement: All animal experiments were carried out after obtaining approval from the Experimental Animal Ethics Committee of Peking University International Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data for this study can be obtained from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Gang Li, MBBS, Chief Physician, Intensive Care Unit, Peking University International Hospital, No. 1 Life Park Road, Zhongguancun Life Science Park, Changping District, Beijing 102206, China.
Received: June 6, 2023
Peer-review started: June 6, 2023
First decision: June 21, 2023
Revised: July 6, 2023
Accepted: July 27, 2023
Article in press: July 27, 2023
Published online: August 19, 2023
Research background

The main pathological feature of Alzheimer’s disease (AD) is the formation of amyloid β-protein (Aβ) plaques in the brain, leading to loss of neuronal synapses, ultimately affecting the patient’s learning and memory abilities. Research has shown that iron death caused by iron overload in nerve cells is an important factor leading to neurodegenerative diseases, and plays a crucial role in the progression of AD. Recently, reports have demonstrated the high selectivity of dexmedetomidine (Dex), an α adrenergic receptor agonist, that can exert neuroprotective effects by inhibiting the release of inflammatory factors, thereby improving cognitive dysfunction in elderly rats.

Research motivation

Currently, there are still no effective drugs to delay the progression of AD, and iron death which may play a crucial role in the progression of this disease is attracting increasing attention from researchers.

Research objectives

To investigate the effect of Dex on iron death in the hippocampus of AD mice by both in vitro and in vivo research.

Research methods

Construction and utilization of an AD model using Aβ. The mouse hippocampal neuronal cell line HT22 was induced, and the levels of cell proliferation activity and intracellular Fe2+ were measured by the cell-counting kit-8 assay and immunofluorescence. The contents of malondialdehyde and glutathione were measured by the TBA method and microplate method, respectively. In the AD mouse model Aβ was injected, and the pathological damage in the mouse hippocampus was detected by hematoxylin and eosin staining and Nissl staining. The Morris water maze was used to evaluate the learning and memory abilities of mice in each group, and protein immunoblotting was used to evaluate the expression levels of p-mammalian target of rapamycin (p-mTOR) and iron death-related proteins transferrin receptor 1 (TFR1), SLC7A11, and glutathione peroxidase 4.

Research results

Dex significantly improved lipid peroxidation and iron influx in mouse hippocampal neurons (HNs) both in vivo and in vitro, and inhibition of the mTOR signaling pathway blocked this process, demonstrating that Dex can inhibit the damage caused by iron death in mouse HNs by activating mTOR-TFR1 signaling regulation, thereby improving cognitive dysfunction in AD mice.

Research conclusions

Dex can significantly activate the mTOR-TFR1 signaling pathway and inhibit iron death in mouse HNs, thereby improving the learning and memory abilities of mice.

Research perspectives

From in vitro and in vivo molecular experimental research, it is possible to analyze the effect of Dex on iron death in AD related nerve cells.