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-HTTLPR ↓ 5-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] |