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©The Author(s) 2022.
World J Psychiatry. Sep 19, 2022; 12(9): 1150-1168
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1150
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1150
Table 4 Epigenetic (DNA methylation, histone tail modifications, and microRNAs) studies on animal models of depressive disorder
| Epigenetic modification | Gene (region)/histone tail modification/miRNA | Alteration | Organism and collected tissue | Ref. |
| DNA methylation | Crf promoter of exon 1 and intronic region between exon 1 and exon 2 (relative to exon 1 start site) | Overall ↑ DNA methylation, and specific ↑ in CpG –147 and CpG –101 site of the Crf gene in stressed female rats in the PVN. No changes in male rats. ↓ DNA methylation in CpG –15 (male and female rats), ↓ DNA methylation in CpG –226, CpG –55 and ↑ in CpG +485 and CpG +494 (male rats) and ↓ DNA methylation in CpG –95 site (female rats) in BNST. ↑ DNA methylation in CpG –232 and CpG –226 (male rats), ↓ CpG –226 and CpG +535 (female) in the CeA | Male and female Wistar-R Amsterdam rats; sacrificed 2 h after stress. Brain tissue (PVN, BNST, CeA) | Sterrenburg et al[93], 2011 |
| DNA methylation | Crf promoter (relative to exon 1 start site) | Chronic social stress induced ↑ DNA methylation in Crf promoter region at CpG site –226 and ↓ DNA methylation level in intronic region of the gene Crf in the PVN. Long term effect of social defeat in mice susceptible to social defeat: ↑ in Crf mRNA levels in PVN and ↓ DNA methylation level at CpG –226, –101, –95, and –79 | Chronically stressed adult mice C57BL/6. Brain tissue (PVN) | Elliott et al[94], 2010 |
| DNA methylation and histone tail modification | Gdnf | ↑ DNA methylation at CpG site 2. ↓ H3ac in NAc of BALB mice and C57BL/6 mice. C57BL/6 mice had higher H3ac and higher Gdnf expression | BALB/c mice with maladaptive response to stressful stimuli and stress resilient strain C57BL/6. Brain tissue (NAc) | Uchida et al[95], 2011 |
| Histone tail modification | H3K14ac | ↓ H3K14ac 1 h after final stress. ↑ H3K14ac 24 h and 10 d after final stress. ↓ Hdac2 mRNA expression 24 h and 15 d after final stress in NAc | Chronically social defeated adult male mice C57BL/6J. Brain tissue (NAc). | Covington et al[11], 2009 |
| Histone tail modification | H3K14ac | H3K14ac ↑ after 24 h and ↓ at longer time in HPC. H3K14ac ↑ after 1 h and 24 h, no changes 10 d and longer in AMG | Chronically social defeated adult male mice C57/BL6J. Brain tissue (HPC and AMG) | Covington et al[96], 2011 |
| Histone tail modification | Bdnf exon IV, H3ac, H4ac | ↓ exon IV Bdnf mRNA. ↓ H3ac and H4ac. ↑ MeCP2 levels. ↑ Hdac mRNA | Rats (early life adversity induced by maternal separation). Brain tissue (HPC) | Seo et al[97], 2016 |
| Histone tail modification | Bdnf III and IV promoter, H3K27me2 | ↑ H3K27me2 at promoter Bdnf III and IV. ↓ total Bdnf mRNA. No change at H3K9me2 | Chronic social defeat stress mice. Brain tissue (HPC) | Tsankova et al[62], 2006 |
| Histone tail modification | H3K9me2 | ↑ H3K9me2 in HPC and mPFC. ↓ Bdnf expression in HPC and mPFC | Wistar rats exposed to maternal separation and chronic unpredicted mild stress. Brain tissue (HPC and mPFC) | Jiang et al[98], 2021 |
| Histone tail modification | H3K4me3, H3K9me3, H3K27me3 | Acute restrain stress: ↑ in H3K9me3 in CA1 and DG; no changes in CA3; ↓ in H3K27me3 in DG and CA1; not significantly altered in CA3. No significant changes for H3K4me3. Subchronic 7-d restraint stress: The basal level of H3K9me3 on day 7 increased in DG, CA1 and CA3. ↓ in H3K9me3 in CA1, CA3 and DG. ↓ in H3K27me3 in DG | Adult male Sprague–Dawley rats (acute stress/7 d restraint stress). Brain tissue (HPC parts: DG, CA1, CA3) | Hunter et al[99], 2009 |
| miRNA | miR Let-7a-1, miR-9, miR-25a/b | ↑ miR Let-7a-1, miR-9, miR-25a/b after acute stress in FCx. No changes in HPC | Male CD1 mice with induced acute or repeated stress. Brain tissue (FCx and HPC) | Rinaldi et al[100], 2010 |
| miRNA | miR-218 | ↓ miR-218 and ↑ DCC in PFC | Chronically social defeated adult male mice C57BL/6. Brain tissue (mPFC) | Torres-Berrío et al[82], 2017 |
| miRNA | miR-16 | ↑ miR-16. ↓ Bdnf mRNA | Sprague-Dawley rats exposed to maternal deprivation. Brain tissue (HPC) | Bai et al[101], 2012 |
| miRNA | 342 miRNAs differently expressed (response to gestational stress) and 336 miRNAs differently expressed in offspring (response to prenatal stress) | ↑ 147 miRNAs and ↓ 195 miRNAs in FCx of female rats. ↑ 205 miRNAs and ↓ 131 miRNAs in offspring | Stress induced through pregnant female Long-Evans rats. Offspring (decapitated 1 to 5 h after parturition). Brain tissue (FCx) | Zucchi et al[102], 2013 |
| miRNA | AMG: 10 miRNAs under acute stress and 28 after chronic stress; HPC CA1: 16 after acute stress and 22 after chronic stress | The overlap: ↑ miR Let-7a-1 in AMG affected by acute and chronic stress. ↑ miR-376b and miR-208, ↓ miR-9 in HPC by acute and chronic stress. Other changes are unique to acute/chronic stress or brain region analyzed | Adult male rats with induced acute or chronic stress. Brain tissue (AMG, HPC CA1 region) | Meerson et al[103], 2010 |
| miRNA | miR-124a, miR-18a, miR-511 | ↑ miR-124a, miR-18a in PFC and HPC persistently. ↓ miR-511 in PFC (in adult rats experienced CUMS) | Adolescent male Wistar rats were stressed with CUMS. Brain tissue (PFC and HPC) | Xu et al[104], 2019 |
- Citation: Šalamon Arčan I, Kouter K, Videtič Paska A. Depressive disorder and antidepressants from an epigenetic point of view. World J Psychiatry 2022; 12(9): 1150-1168
- URL: https://www.wjgnet.com/2220-3206/full/v12/i9/1150.htm
- DOI: https://dx.doi.org/10.5498/wjp.v12.i9.1150