title: Genetic deletion of the Histone Deacetylase 6 exacerbates selected behavioral deficits in the R6/1 mouse model for Huntington's disease.
abstract: BACKGROUND
  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.
authors.affiliation: 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.
authors.forename: Alienor
authors.initials: A
authors.lastname: Ragot
authors.affiliation: 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.
authors.forename: Susanna
authors.initials: S
authors.lastname: Pietropaolo
authors.affiliation: 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.
authors.forename: Jean
authors.initials: J
authors.lastname: Vincent
authors.affiliation: 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.
authors.forename: Pauline
authors.initials: P
authors.lastname: Delage
authors.affiliation: University of Bordeaux 146, rue Léo-Saignat, 33077, Bordeaux, France ; Interdisciplinary Institute for Neuroscience, CNRS UMR 5297 33000, Bordeaux, France.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Faculté de Médecine, Laboratoire INSERM, UMR 894- Université Paris Descartes, Sorbonne Paris Cité Paris, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Allinquant
authors.affiliation: University of Bordeaux 146, rue Léo-Saignat, 33077, Bordeaux, France ; Neurocentre Magendie 146, rue Léo-Saignat, 33077, Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leinekugel
authors.affiliation: 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.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: 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.
authors.forename: Yoon H
authors.initials: YH
authors.lastname: Cho
mesh_terms: D000107:Acetylation; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D017353:Gene Deletion; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006816:Huntington Disease / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D014404:Tubulin; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: Brain-derived neurotrophic factor; cognitive behavior; epigenetics