Neurocentre Magendie

Jean VINCENT




ITA

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1 publication(s) depuis Septembre 2015:


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09/2015 | brain behav   IF 2.1
Genetic deletion of the Histone Deacetylase 6 exacerbates selected behavioral deficits in the R6/1 mouse model for Huntington's disease.
Ragot A, Pietropaolo S, Vincent J, Delage P, Zhang H, Allinquant B, Leinekugel X, Fischer A, Cho YH

Abstract:
INTRODUCTION: The inhibition of the Histone Deacetylase 6 (HDAC6) increases tubulin acetylation, thus stimulating intracellular vesicle trafficking and brain-derived neurotrophic factor (BDNF) release, that is, cellular processes markedly reduced in Huntington's disease (HD). METHODS: We therefore tested that reducing HDAC6 levels by genetic manipulation would attenuate early cognitive and behavioral deficits in R6/1 mice, a mouse model which develops progressive HD-related phenotypes. RESULTS: In contrast to our initial hypothesis, the genetic deletion of HDAC6 did not reduce the weight loss or the deficits in cognitive abilities and nest-building behavior shown by R6/1 mice, and even worsened their social impairments, hypolocomotion in the Y-maze, and reduced ultrasonic vocalizations. CONCLUSIONS: These results weaken the validity of HDAC6 reduction as a possible therapeutic strategy for HD. The data are discussed in terms of additional cellular consequences and anatomical specificity of HDAC6 that could explain these unexpected effects.