Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders

Shahid Mohammad, Stephen J. Page, Li Wang, Seiji Ishii, Peijun Li, Toru Sasaki, Aiesha Basha, Anna Salzberg, Zenaide Quezado, Fumiaki Imamura, Hirotaka Nishi, Keiichi Isaka, Joshua G. Corbin, Judy S. Liu, Yuka Imamura Kawasawa, Masaaki Torii, Kazue Hashimoto-Torii

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Abstract

Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. These include fetal alcohol spectrum disorders (FASDs) with a wide range of cognitive deficiencies, including impaired motor skill development. Although these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells altered gene expression in their descendant neurons. Among the altered genes, an increase of the calcium-activated potassium channel Kcnn2 in the motor cortex correlated with motor learning deficits in a mouse model of FASD. Pharmacologic blockade of Kcnn2 improves these learning deficits, suggesting Kcnn2 blockers as a new intervention for learning disabilities in FASD.

Original languageEnglish (US)
Pages (from-to)533-543
Number of pages11
JournalNature Neuroscience
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2020

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Mohammad, S., Page, S. J., Wang, L., Ishii, S., Li, P., Sasaki, T., Basha, A., Salzberg, A., Quezado, Z., Imamura, F., Nishi, H., Isaka, K., Corbin, J. G., Liu, J. S., Kawasawa, Y. I., Torii, M., & Hashimoto-Torii, K. (2020). Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders. Nature Neuroscience, 23(4), 533-543. https://doi.org/10.1038/s41593-020-0592-z