Activity-dependent Signaling and Epigenetic Abnormalities in Mice Exposed to Postnatal Ethanol

Neuroscience
Shivakumar SubbannaBalapal S Basavarajappa

Abstract

Postnatal ethanol exposure has been shown to cause persistent defects in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms responsible for these abnormalities are less well studied. We evaluated the influence of postnatal ethanol exposure on several signaling and epigenetic changes and on expression of the activity-regulated cytoskeletal (Arc) protein in the hippocampus of adult offspring under baseline conditions and after a Y-maze spatial memory (SP) behavior (activity). Postnatal ethanol treatment impaired pCaMKIV and pCREB in naïve mice without affecting H4K8ac, H3K14ac and H3K9me2 levels. The Y-maze increased pCaMKIV, pCREB, H4K8ac and H3K14ac levels in saline-treated mice but not in ethanol-treated mice; while H3K9me2 levels were enhanced in ethanol-exposed animals compared to saline groups. Like previous observations, ethanol not only reduced Arc expression in naïve mice but also behaviorally induced Arc expression. ChIP results suggested that reduced H3K14ac and H4K8ac in the Arc gene promoter is because of impaired CBP, and increased H3K9me2 is due to the enhanced recruitment of G9a. The CB1R antagonist and a G9a/GLP inhibitor, which were shown to rescue postnatal ethano...Continue Reading

Citations

Jul 3, 2019·British Journal of Pharmacology·Balapal S BasavarajappaShivakumar Subbanna
Mar 15, 2020·The International Journal of Neuropsychopharmacology·Madhu ShivakumarBalapal S Basavarajappa
Aug 26, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Vikram JoshiBalapal S Basavarajappa
May 1, 2021·International Journal of Molecular Sciences·Balapal S Basavarajappa, Shivakumar Subbanna

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