Table 2.

Gene-based pharmacoepigenetic studies of antidepressants in rodents

Gene	Epigenetic Mark	Baseline or Post-treatment	Antidepressant	Species/strain, model	Tissue	Outcome	Reference
Bdnf	5mC within promoter IV	Post-treatment	Fluoxetine	C57BL/6 J mice, post-stroke depression model	Hippocampus	↑5mC in 2 CpG sites ↑ Bdnf expression ↓ depression-like behaviors	Jin et al. (2017)
	H4K12ac within promoter III	Post-treatment	Fluoxetine + HDAC inhibitor	Balb/c mice, infant maternal separation	Forebrain neocortex	↑ H4K12ac ↑ Bdnf expression ↓ depression-like behaviors	Schmauss (2015)
	H3ac within promoter III and IV	Post-treatment	Imipramine	Adult male Bl6/C57 mice, chronic social stress model	Hippocampus	↑ H3ac within promoters III and VI ↑ Bdnf IV expression	Tsankova et al. (2006)
	H3K9me2 downstream of exon IV	Post-treatment	Tranylcypromine	C57BL/6J mice, social stress model	mPFC	↓ H3K9me2 ↑ Bdnf IV expression reversed cognitive inflexibility of social stress	Xu et al. (2018)
	5mC within promoter	Post-treatment	Genipin	PRS mice (offspring of prenatally stressed dams)	Hippocampus	5mC demethylation through inhibition of DNMT1 normalized Bdnf expression reversed depressive-like behaviors	Ye et al. (2018)
	-	Post-treatment	SAHA	Crtc1(-/) mice	PFC	↑ Bdnf IV expression partially rescued depressive-like behavior	Meylan et al. (2016)
Htr1a	5mC within promoter	Post-treatment	Imipramine	Adult male BALB/c Mice exposed to unpredictable chronic mild stress	PFC, midbrain	↓ 5mC of 1 CpG reversed depressive-like phenotype	Le Francois et al. (2015)
S100a10	5mC within promoter	Post-treatment	Escitalopram	Female FSL rodent model of depression	PFC	↓ 5mC ↑ S100a10 expression	Melas et al. (2012)
Crf	5mC within promoter	Post-treatment	Imipramine	Adult mice exposed to social defeat	Hypothalamus	↑ 5mC at 5 CpGs ↓ Crf expression ↓ social avoidance behavior	Elliott et al. (2010)
Nr2b	H3K9ac and H3K27ac within promoter	Post-treatment	Imipramine	Mouse fetuses	Neocortical neurons	↑ H3ac ↑ Nrb2 expression ↓ HDAC3 and HDAC4 activity	Nghia et al. (2015)
Grm2	H3K27ac within promoter	Post-treatment	LAC	FSL rodent model of depression	Hippocampus, PFC	↑ H3K27ac ↑ Grm2 expression	Nasca et al. (2013)

Abbreviations: 5mC – 5-methylcytosine; Bdnf – brain-derived neurotrophic factor; Crf – corticotrophin-releasing factor; FSL – Flinders Sensitive Line; Grm2 – glutamate metabotropic receptor type; H3ac – histone 3 acetylation; H3K9me2 – histone 3 lysine 9 dimethylation; H4K12ac – histone 4 lysine 12 acetylation; H3K9ac – histone 3 lysine 9 acetylation; HDAC – histone deacetylase; Htr1a – 5-Hydroxytryptamine receptor 1A; LAC – L-acetylcarnitine; Nr2b – N-methyl D-aspartate receptor subtype 2B; PFC – prefrontal cortex; S100a10 – S100 Calcium Binding Protein A10; SAHA – suberoylanilide hydroxamic acid.