TY - JOUR
T1 - Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders
AU - Mohammad, Shahid
AU - Page, Stephen J.
AU - Wang, Li
AU - Ishii, Seiji
AU - Li, Peijun
AU - Sasaki, Toru
AU - Basha, Aiesha
AU - Salzberg, Anna
AU - Quezado, Zenaide
AU - Imamura, Fumiaki
AU - Nishi, Hirotaka
AU - Isaka, Keiichi
AU - Corbin, Joshua G.
AU - Liu, Judy S.
AU - Kawasawa, Yuka Imamura
AU - Torii, Masaaki
AU - Hashimoto-Torii, Kazue
N1 - Funding Information:
We thank A. Wafa Syed and S. Bhuvanendran for technical assistance. We also thank A. I. Son for critical reading of the manuscript. This work was supported by National Institutes of Health grants R01AA025215 (to K.H.-T.), R01AA026272 (to M.T. and K.H.-T.) and UH2AA026106 as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (to K.H.-T. and M.T.). The study was also funded by the Scott-Gentle Foundation (to K.H.-T. and M.T.). This study was supported by award 1U54HD090257-01 from the the National Institutes of Health, District of Columbia Intellectual and Developmental Disabilities Research Center award program.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41593-020-0592-z
DO - 10.1038/s41593-020-0592-z
M3 - Article
C2 - 32203497
AN - SCOPUS:85082809605
SN - 1097-6256
VL - 23
SP - 533
EP - 543
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 4
ER -