Genetic deletion of the Histone Deacetylase 6 exacerbates selected behavioral deficits in the R6/1 mouse model for Huntington's disease

Brain and Behavior

Alienor Ragot²  Susanna Pietropaolo²  Jean Vincent²  Pauline Delage²  Hongyu Zhang¹  Bernadette Allinquant³  Xavier Leinekugel¹  André Fischer⁴ 

[1] University of Bordeaux, Bordeaux, France;Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287, Talence Cedex, France;Faculté de Médecine, Laboratoire INSERM, UMR 894- Université Paris Descartes, Sorbonne Paris Cité, Paris, France;Department for Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany

关键词: Brain‐derived neurotrophic factor;    cognitive behavior;    epigenetics;   

DOI  :  10.1002/brb3.361

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 INCIA, CNRS UMR 5287. Brain and Behavior published by Wiley Periodicals, Inc.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.