A single binge ethanol exposure is apoptotic within hours across neurodevelopment and partially regulated by the Myt1l gene.

Fuhler, N.; Palmer, C.; Tunzi, G.; Tian, L.; Fotedar, M.; Chase, R.; Prakasam, R.; Maloney, S. E.; Neblock, C. E.; Chen, J.; Kroll, K. L.; Dougherty, J. D.; Noguchi, K.

doi:10.1101/2025.06.27.662020

bioRxiv · 10.1101/2025.06.27.662020

A single binge ethanol exposure is apoptotic within hours across neurodevelopment and partially regulated by the Myt1l gene.

Fuhler, N.·Palmer, C.·Tunzi, G.·Tian, L.·Fotedar, M.·Chase, R.·Prakasam, R.·Maloney, S. E.·Neblock, C. E.·Chen, J.·Kroll, K. L.·Dougherty, J. D.·Noguchi, K.

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Abstract

Ethanol rapidly produces widespread neuronal apoptosis during early development, but this susceptibility declines as the brain matures. In previous research, we found Myt1l (a proneuronal transcription factor) mutations can cause precocious differentiation, neuronal immaturity, and transcriptomic alterations, including many in apoptotic regulators. Therefore, we used a recently developed Myt1l haploinsufficient mouse model to examine this genes effects on ethanol-induced apoptosis across different developmental stages. We discovered that haploinsufficiency can moderately influence vulnerability to ethanol in a complex, age- and cell type-specific manner: apoptosis was reduced on P7, increased P21, but unaffected on P60. Remarkably, we also discovered the previously unrecognized ability of a single binge of ethanol to rapidly increase apoptosis within six hours in early adolescent and adult wild-type mice occurring in microglia and the newborn granule neurons in the hippocampus. This suggests apoptosis is an underappreciated contributor to ethanols neuropathology at older ages and, translated to human use, occurs far more frequently than previously recognized.

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Fuhler, N., Palmer, C., Tunzi, G., Tian, L., Fotedar, M., Chase, R., Prakasam, R., Maloney, S. E., Neblock, C. E., Chen, J., Kroll, K. L., Dougherty, J. D., Noguchi, K.. 2025-06-29. A single binge ethanol exposure is apoptotic within hours across neurodevelopment and partially regulated by the Myt1l gene.. https://doi.org/10.1101/2025.06.27.662020

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