The Department of Biomedicine

BBB seminar: Hermes Hsiao-Mei Yeh

Prenatal alcohol exposure, GABA, and enduring interneuronopathy in the prefrontal cortex

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Hermes Hsiao-Mei Yeh
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

Consumption of alcohol (ethanol) during pregnancy can have profound and enduring adverse consequences on the offspring, including compromised cognition and other neurodevelopmental abnormalities. Preventable as it is by abstinence during pregnancy, and despite public outreach and awareness, a significant percentage of women continue to drink during pregnancy, some even binge drink to risky levels. Ethanol readily crosses the placenta and distributes to all fetal organs, notably the brain.

Gestational exposure to ethanol has been reported to alter the disposition of tangentially migrating GABAergic (inhibitory) cortical interneurons in the fetus, but much remains to be elucidated. We have established that the tangential migration of interneurons is regulated in part by the developmental neurotransmitter, GABA, and that the migration process is a proximal target of ethanol, a canonical allosteric modulator of the GABAA receptor. We established further that the aberrant tangential migration of GABAergic interneurons as a result of prenatal exposure to ethanol persisted as an enduring interneuronopathy in the brain of the offspring, notably the medial prefrontal cortex. Our findings underscore that aberrant neuronal migration, inhibitory/excitatory imbalance, and thus interneuronopathy, contribute to indelible abnormal cortical circuit form and function in fetal alcohol spectrum disorders.

We use a multidisciplinary approach to elucidate the cellular and subcellular underpinnings of the interneuronopathy associated with in utero ethanol exposure. Our work aims to establish the groundwork for future investigations on the neurodevelopmental effects of in utero ethanol exposure on cortical form and function, cognitive and behavioral outcomes and, ultimately, on their therapeutic management.

Chairperson: Meg Veruki, Department of Biomedicine