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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-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