An adverse maternal environment (AME) and Western diet (WD) in early life predispose offspring toward cognitive impairment in humans and mice. Cognitive impairment associates with hippocampal dysfunction. An important regulator of hippocampal function is the hippocampal Nociceptin/Orphanin FQ (N/OFQ) system. Previous studies find links between dysregulation of hippocampal N/OFQ receptor (NOP) expression and impaired cognitive function. NOP is encoded by the opioid receptor-like 1 (Oprl1) gene that contains multiple mRNA variants and isoforms. Regulation of Oprl1 expression includes histone modifications within the promoter. We tested the hypothesis that an AME and a postweaning WD increase the expression of hippocampal Oprl1 and select variants concurrent with altered histone code in the promoter. We created an AME-WD model combining maternal WD and prenatal environmental stress plus postweaning WD in the mouse. We analyzed the hippocampal expression of Oprl1, Oprl1 variants, and histone modifications in the Oprl1 promoter in offspring at postnatal day (P) 21 and P100. An AME and an AME-WD significantly increased the total hippocampal expression of Oprl1 and variant V4 concurrently with an increased accumulation of active histone marks in the promoter of male offspring. We concluded that an AME and an AME-WD alter hippocampal Oprl1 expression in offspring through an epigenetic mechanism in a variant-specific and sex-specific manner. Altered hippocampal Oprl1 expression may contribute to cognitive impairment seen in adult males in this model. Epigenetic regulation of Oprl1 is a potential mechanism by which an AME and a WD may contribute to neurocognitive impairment in male offspring.
Anat Rec (Hoboken)
Humans; Male; Animals; Mice; Epigenesis, Genetic
Oprl1 variants; adverse maternal environment; hippocampus; histone modifications
Ke X, Huang Y, Fu Q, Majnik A, Sampath V, Lane RH. Adverse maternal environment alters Oprl1 variant expression in mouse hippocampus. Anat Rec (Hoboken). 2023;306(1):162-175. doi:10.1002/ar.25056
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Publisher's Link: https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/ar.25056