Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum |
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Authors: | Guo Weixiang Crossey Erin L Zhang Li Zucca Stefano George Olivia L Valenzuela C Fernando Zhao Xinyu |
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Institution: | Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America. |
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Abstract: | BackgroundFetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear.Methodology/Principal FindingsWe demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the developing cerebellar cortex of naïve rats. We also show that exposure to ethanol during the 3rd trimester-equivalent of human pregnancy reduces CBP levels. CBP is a histone acetyltransferase, a component of the epigenetic mechanism controlling neuronal gene expression. We further demonstrate that the acetylation of both histone H3 and H4 is reduced in the cerebellum of ethanol- treated rats.Conclusions/SignificanceThese findings indicate that ethanol exposure decreases the expression and function of CBP in the developing cerebellum. This effect of ethanol may be responsible for the motor coordination deficits that characterize fetal alcohol spectrum disorders. |
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