Genetic deletion of the Histone Deacetylase 6 exacerbates selected behavioral deficits in the R6/1 mouse model for Huntington’s disease.
Brain Behav. 2015-06-24; 5(9): n/a-n/a
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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).
(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,
(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,
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.
PMID: 26445700 [Indexed for MEDLINE]