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Ethanol-Induced Changes in Brain of Transgenic Mice Overexpressing DYRK1A

Abstract : Alcoholism is a chronic relapsing disorder defined by loss of control over excessive consumption of ethanol despite damaging effects on the liver and brain. We previously showed that the overexpression in mice of Dyrk1A (TgDyrk1A, for dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A) reduces the severity of alcohol mediated liver injury. Ethanol consumption has also been associated with increased brain glutamate concentration that led to therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Interestingly, mice overexpressing Dyrk1A (TgDyrk1A mice) present a reduction of glutamatergic brain transmission, which we propose could be protective against alcohol intake. To answer this question, we investigated the ethanol preference in TgDyrk1A mice using a two-bottle choice paradigm. TgDyrk1A mice showed a non-significant decrease of voluntary ethanol intake and ethanol preference compared with wild-type mice. At the peripheral level, mice overexpressing Dyrk1A show lower ethanol plasma levels, indicating a faster ethanol metabolism. At the end of the protocol, lasting 21 days, brains were extracted for protein analysis. Ethanol reduced levels of the synaptic protein PSD-95 and increased the glutamate decarboxylase GAD65, specifically in the cortex of TgDyrk1A mice. Our results suggest that overexpression of DYRK1A may cause different ethanol-induced changes in the brain.
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https://hal-cnrs.archives-ouvertes.fr/hal-03300422
Contributor : Colette Orange <>
Submitted on : Tuesday, July 27, 2021 - 10:15:54 AM
Last modification on : Thursday, July 29, 2021 - 3:58:27 AM

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Marta Fructuoso, Yu Chen Gu, Nadim Kassis, Maria Martinez de Lagran, Mara Dierssen, et al.. Ethanol-Induced Changes in Brain of Transgenic Mice Overexpressing DYRK1A. Molecular Neurobiology, Humana Press, 2020, 57 (7), pp.3195-3205. ⟨10.1007/s12035-020-01967-6⟩. ⟨hal-03300422⟩

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