Alterations in depression and stress reactivity in mice with a knockout of MeCP2 in POMC neurons

Methyl-CpG binding protein 2 (MeCP2) is a neuroepigenetic factor, implicated in the pathophysiology of obesity. Previous work has shown that forebrain knockout (KO) of MeCP2 leads to an overweight phenotype in mice given chronic exposure to high fat diet. Our lab has recently shown that knocking out MeCP2 specifically in pro-opiomelanocortin (POMC) neurons of the hypothalamus also produces an overweight phenotype as well as increased plasma corticosterone levels, a stress hormone that can become deleterious when chronically elevated (Frayre et al 2024). Based on these data, we sought to determine if POMC-Cre MeCP2 KO mice were more sensitive to the effects of early life stress (ELS) using a mouse model of maternal separation (MS). Behavioral assessments and immunoassay analyses were conducted to evaluate depression- and anxiety-like behaviors, enabling the investigation of ELS effects in KO and wild-type (WT) mice. Our current data suggest that ELS MS produces anxiety-like behavior in WT mice relative to WT mice in non-MS group and that POMC-MeCP2 KO mice may be resistant to ELS MS with regard to anxiety- and depression-like phenotypes. Taken together, it is possible that POMC-MeCP2 KO mice may produce mechanistic changes that blunt the early effects of maternal stress. NIGMS 1SC1GM44190-01 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.