Skip to main content

Advertisement

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-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]
  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