Maternal separation alters serotonergic and HPA axis gene expression independent of separation duration in mice.

ABSTRACT

Adverse early life experiences (aELEs), such as child abuse, neglect, or trauma, increase lifetime vulnerability for mental illness. In this study, aELEs were modeled in c57bl/6 mice using the maternal separation (MS) paradigm, in which pups were separated for 180 min/day (MS180), 15 min/day (MS15), or left undisturbed (AFR) from postnatal day 2-14. As adults, pups that experienced MS15 or MS180 demonstrated decreases in tryptophan hydroxylase 2 and serotonin transporter mRNA in the dorsal raphe dorsalis and ventralis, and increases in glucocorticoid receptor mRNA in the dentate gyrus of the hippocampus. To investigate factors underlying shared expression between MS conditions, dam on-nest time and DNA methylation at the TPH2 promoter and 5' UTR were assessed. Post-reunion on-nest time increased as a function of separation duration, potentially serving as a mitigating factor underlying similar expression between MS conditions. TPH2 DNA methylation remained unchanged, suggesting changes in TPH2 mRNA are not mediated by changes in DNA methylation of this region. The shared pattern of expression between MS15 and MS180 conditions suggests a species- or strain- specific response to MS unique to c57bl/6 mice.