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Table 3 Early stress-induced epigenetic modifications in other candidate genes

From: Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders

Candidate gene Objective Model/tissue type Early stress/assessment age Epigenetic and expression changes Interpretation References
Er-α Determine the effect of maternal care on Er-α mRNA exp and Erα1b promoter methylation Long-Evans hooded rats MPOA of Amygdala Maternal care variations: high vs low LG-ABN Assessed: PND6 Erα1b promoter methylation in high vs low LG-ABN offspring ↑ Stat5 binding to Erα1b promoter in high vs low LG-ABN offspring ↑ Er-α mRNA exp in high vs low LG-ABN offspring Higher levels of maternal care cause ↓Erα1b promoter methylation, ↑Er-α mRNA exp and ↑ Stat5 binding to Erα1b promoter in the MPOA in Long-Evans hooded rats on PND6 [59]
5-HTT Determine the relationship between early stress and 5-HTT gene methylation Rhesus macaques Peripheral blood DNA Rearing variations: MR vs NR Assessed: 90–120 days (infants) ↑ average 5-HTT gene methylation in carrier of the low-expressing rh5-HTTLPR5-HTT mRNA in PBMCs Variations in maternal care were associated with average differences in 5-HTT gene methylation and this was dependent on the 5-HTT polymorphism in Rhesus macaques [57]
Determine the effect of early stress on 5-HTT gene and whole genome DNA methylation F bonnet macaques Peripheral blood DNA VFD from 3–8 months age Assessed: mean = 8.4 years 5-HTT and whole genome methylation ↑ 5-HTT and whole genome methylation ↑ stress reactivity in VFD 5-HTT gene and whole genome methylation confer an ↑ stress reactivity following early stress in adolescent F bonnet macaques [58]
Gad1 Determine the effect of maternal care on the Gad1 promoter in the hippocampus Long-Evans hooded rats Hippocampus Maternal care variations: high vs low LG-ABN Assessed: 3–4 months of age except for NGFI-A association to Gad1 promoter at PND4 ↓ methylation of Gad1 promoter in high vs low LG-ABN offspring ↑ histone H3K9 acetylation of Gad1 promoter in high vs low LG-ABN offspring ↑ NGFI-A association w Gad1 promoter in high vs low LG-ABN offspring ↑ Gad1 mRNA exp in high vs low LG-ABN offspring High levels of maternal care ↓ Gad1 promoter methylation, ↑ Gad1 promoter histone acetylation and ↑ Gad1 mRNA in the hippocampus of Long-Evans hooded rats [66]
Bdnf Determine the effect of early stress on DNA methylation Long-Evans hooded rats Hippocampus and PFC Exposure to abusive or caring mother from PND1–7 for 30 min Assessed: PND8, 30 and 90 ↑ methylation of Bdnf exon IV and IX in PFC ↓ Bdnf mRNA exp in PFC ↑ Bdnf mRNA exp in hippocampus Early abuse ↑ methylation of Bdnf exon IV and IX in the PFC that persists into adulthood in Long-Evans hooded rats [53]
Determine the effect of early stress on Bdnf mRNA, protein and miR-16 exp Sprague Dawley rats Hippocampus MS: PND1–13 CUPS: 10–13 weeks C: no stress Assessed: 13–14 weeks Only Bdnf transcribed from 5ʹ exon VI and 3ʹ common exon analysed Bdnf mRNA exp in MS vs CUPS and C ↓ Bdnf protein in MS vs CUPS and C ↑ miR-16 exp in MS vs CUPS and C ↓ Bdnf mRNA exp in MS correlated significantly with ↑ miR-16 exp MS induced significantly different BDNF and miR-16 expression in rats. [54]
BDNF and miR-16 levels were inversely related in the presence of early stress
Reelin (Reln) Determine the effect of MS on Reln expression Wistar rats Hippocampus MS: PND2–15 for 3 h Assessed: PND22 Reln gene methylation ↓ Reln mRNA exp MS ↑ Reln gene methylation and ↓ Reln mRNA exp in Wistar rats on PND22 [67]
  1. ↑ increased, ↓ decreased, ↔ no change, 5-HTT serotonin transporter, PND postnatal day, Bdnf brain-derived neurotrophic factor, DNA deoxyribonucleic acid, Er-α estrogen receptor alpha, exp expression, F female, Gad1 glutamic acid decarboxylase 1, LG-ABN licking grooming arched-back nursing, MPOA medial preoptic area, MR mother reared, NR nursery reared, mRNA messenger ribonucleic acid, PBMC peripheral blood mononuclear cells, VFD variable foraging demand, MS maternal separation, NGFI-A nerve growth factor inducible protein A, PFC prefrontal cortex, PND postnatal day, Stat5 signal transducer and activator of transcription 5, mi-R micro-RNA, CUPS chronic unpredictable stress, C control