Early life stress induces a transient increase in hippocampal corticotropin‐releasing hormone in rat neonates that precedes the effects on hypothalamic neuropeptides

Abstract

Early life stress (ELS) programs hypothalamus‐pituitary‐adrenal (HPA) axis activity and affects synaptic plasticity and cognitive performance in adults; however, the effects of ELS during the temporal window of vulnerability are poorly understood. This study aimed to thoroughly characterize the effects of ELS in the form of periodic maternal separation (MS180) during the time of exposure to stress. Hippocampal corticotropin‐releasing hormone (CRH) gene expression and baseline HPA axis activity were analyzed at postnatal (P) days 6, 12, 15, and 21, and in adulthood (P75); these factors were correlated with plasticity markers and adult behavior. Our results indicate that MS180 induces an increase in hippocampal CRH expression at P9, P12, and P15, whereas an increase in hypothalamic CRH expression was observed from P12 to P21. Increased arginine‐vasopressin expression and corticosterone levels were observed only at P21. Moreover, MS180 caused transient alterations in hypothalamic synaptophysin expression during early life. As adults, MS180 rats showed a passive coping strategy in the forced swimming test, cognitive impairments in the object location test, increased hypothalamic CRH expression, and decreased oxytocin (OXT) expression. Spearman's analysis indicated that cognitive impairments correlated with CRH and OXT expression. In conclusion, our data indicate that MS180 induces a transient increase in hippocampal CRH expression in neonates that precedes the effects on hypothalamic neuropeptides, confirming the role of increased CRH during the temporal window of vulnerability as a mediator of some of the detrimental effects of ELS on brain development and adult behavior.

EJN stress, brain and behaviour special issue

“…One is certainly the timing of the stressful challenge and the context. Especially early in life exposure to adversity has lasting impacts on brain and behaviour (Čater & Majdič, 2021; Clinton et al, 2021; Roque et al, 2021; Wang et al, 2021), specifically also with regard to addiction and reward circuitry (Roque et al, 2021; Rudolph et al, 2020; Levis et al, 2021; Mooney‐Leber et al, 2021), pain responding (Melchior et al, 2021), epigenetic programming (Alyamani et al, 2021; Womersley et al, 2021), neuroinflammation (Friend et al, 2020; Marsland et al, 2021) and in interaction with the metabolic regulation (Berry et al, 2021). Beyond this, it is even unclear how ‘normative’ developmental experiences contribute to stress‐related behaviours (Farber et al, 2020), but it may be that broader environmental factors, such as access to green space, may contribute to resilience and reduced stress responding (Rojas‐Carvajal et al, 2021).…”