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

• Published in: The European journal of neuroscience 2022-05, Vol.55 (9-10), p.2108-2121
• Main Authors: Roque, Angélica, Valles Méndez, Kinberli Marcela, Ruiz, Roberto, Pineda, Edel, Lajud, Naima, Vaidya, Vidita
• Format: Article
• Language: English
• Subjects: Adults; Animals; Cognitive ability; Corticosterone; Corticosterone - metabolism; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - metabolism; Cyclin-dependent kinase inhibitor p21; Gene expression; Hippocampus; Hippocampus - metabolism; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - metabolism; Hypothalamus; Hypothalamus - metabolism; Maternal Deprivation; maternal separation; Neonates; Neuropeptides; Neuropeptides - metabolism; Oxytocin; Pituitary; Pituitary-Adrenal System - metabolism; Rats; Stress, Psychological - metabolism; Synaptic plasticity; Synaptophysin; Vasopressin
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15193

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. Early life stress in the form of MS180 induces a transient increase in hippocampal CRH (red line) expression in neonates that precedes the effects on hypothalamic CRH (blue line). Additionally, an increase in hypothalamic AVP (green line) and plasma CORT (purple line) was observed at weaning. The findings confirm the role of increased CRH during vulnerable time windows as a mediator of some of the detrimental effects of ELS on brain development and adult behavior.