Adverse maternal environment alters Oprl1 variant expression in mouse hippocampus

Area of Science:

• Neuroscience
• Epigenetics
• Developmental Biology

Background:

• Adverse maternal environment (AME) and Western diet (WD) are linked to cognitive impairment in offspring.
• Hippocampal dysfunction and dysregulation of the Nociceptin/Orphanin FQ (N/OFQ) system are associated with cognitive deficits.
• The NOP receptor, encoded by the Oprl1 gene, has multiple mRNA variants and its expression is regulated by histone modifications.

Purpose of the Study:

• To investigate the effects of AME and WD on hippocampal Oprl1 expression and its epigenetic regulation in offspring.
• To determine if AME and WD alter specific Oprl1 mRNA variants and histone modifications in the Oprl1 promoter.
• To explore the sex-specific effects of AME and WD on Oprl1 expression and epigenetic marks.

Main Methods:

• Development of a combined AME-WD mouse model.
• Analysis of hippocampal Oprl1 expression, including specific variants, at postnatal days 21 and 100.
• Assessment of histone modifications within the Oprl1 promoter region.

Main Results:

• AME and AME-WD significantly increased total hippocampal Oprl1 expression and variant V4 in male offspring.
• An increased accumulation of active histone marks was observed in the Oprl1 promoter of male offspring.
• These changes were observed at both postnatal day 21 and 100.

Conclusions:

• AME and AME-WD epigenetically alter hippocampal Oprl1 expression in a variant-specific and sex-specific manner in male offspring.
• Altered hippocampal Oprl1 expression may contribute to cognitive impairment observed in adult males exposed to AME and WD.
• Epigenetic regulation of Oprl1 presents a potential mechanism linking adverse early-life environments to neurocognitive impairment in male offspring.