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

Alienor Ragot, Susanna Pietropaolo, Jean Vincent, Pauline Delage, Hongyu Zhang, Bernadette Allinquant, Xavier Leinekugel, André Fischer, Yoon H. Cho
Brain Behav. 2015-06-24; 5(9): n/a-n/a
DOI: 10.1002/brb3.361

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1. Brain Behav. 2015 Sep;5(9):e00361. doi: 10.1002/brb3.361. Epub 2015 Jun 24.

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

Ragot A(1), Pietropaolo S(1), Vincent J(1), Delage P(1), Zhang H(2), Allinquant
B(3), Leinekugel X(4), Fischer A(5), Cho YH(1).

Author information:
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR
5287 Avenue des Facultés, 33405, Talence Cedex, France ; University of Bordeaux
146, rue Léo-Saignat, 33077, Bordeaux, France.
(2)University of Bordeaux 146, rue Léo-Saignat, 33077, Bordeaux, France ;
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297 33000, Bordeaux,
France.
(3)Faculté de Médecine, Laboratoire INSERM, UMR 894- Université Paris Descartes,
Sorbonne Paris Cité Paris, France.
(4)University of Bordeaux 146, rue Léo-Saignat, 33077, Bordeaux, France ;
Neurocentre Magendie 146, rue Léo-Saignat, 33077, Bordeaux, France.
(5)Department for Psychiatry and Psychotherapy, University Medical Center
Göttingen Grisebachstr. 5, 37077, Göttingen, Germany ; German Center for
Neurodegenerative Diseases (DZNE) Göttingen Grisebachstr. 5, 37077, Göttingen,
Germany.

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.

DOI: 10.1002/brb3.361
PMCID: PMC4589808
PMID: 26445700 [Indexed for MEDLINE]


Auteurs Bordeaux Neurocampus