Abstract
Chronic stress during early life, such as exposure to social conflict or deficits in parental care, can have persistent adverse behavioural effects. Offspring in a rodent model of maternal depression and early life stress have increased susceptibility to maternal depression themselves, suggesting a pathway by which maternal stress could be intergenerationally inherited. The overall aim of this study was to explore the genetic regulatory pathways underlying how maternal social stress and reduced care mediates stress-related behavioural changes in offspring across generations. This study investigated a social stress-based rat model of postpartum depression and the intergenerational inheritance of depressed maternal care where F0 (dams exposed to male intruder stress during lactation) and F1 offspring are directly exposed to social stress. RNASeq was used to investigate genome-wide transcriptome changes in the hippocampus of F1 and F2 generations. Transcriptome analyses revealed differential expression of 69 genes in the F1 generation and 14 in the F2 between controls versus social stress differences. Many of these genes were receptors and calcium-binding proteins in the F1 and involved in cellular oxidant detoxification in F2. The present data identify and characterize changes in the neural expression of key genes involved in the regulation of depression maintained between the generations, suggesting a potential neural pathway for the intergenerational transmission of depressed maternal care and maternal anxiety in the CSS model. Further work is needed to understand to what extent these results are due to molecular germline inheritance and/or the social propagation of deficits in maternal care.
Highlights
Chronic stress during early life, such as exposure to prenatal and postnatal depression or deficits in parental care, can have persistent adverse behavioural effects (MurgatroydEdited by: Mathias Schmidt et al, 2010, 2015; Peña et al, 2017)
This study investigated a social stress-based rat model of postpartum depression and the intergenerational inheritance of depressed maternal care where F0 and F1 offspring are directly exposed to social stress
We have previously reported that methylation patterns of Nr3c1 gene are altered in the brains of F1 dams but not the F2 dams of the chronic social stress (CSS) rat model of postpartum depression and early-life stress (Nephew et al, 2017)
Summary
Chronic stress during early life, such as exposure to prenatal and postnatal depression or deficits in parental care, can have persistent adverse behavioural effects In contrast to the Nr3c1 methylation patterns, peripheral levels of intracellular adhesion protein 1 (ICAM-1 ) are up-regulated in the F2 dams, but not the F1 animals (Murgatroyd et al, 2016) These data suggest that there are variations in gene regulation between the generations, possibly switching from stress to immune regulatory pathways. We assessed the presence of genome-wide changes in hippocampal gene expression following exposure to CSS in the F1 and F2 dams in this rodent model of maternal depression and early-life social stress and determined whether there were specific genes and/or shared pathways that are intergenerationally affected by stress
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