Abstract | INTRODUCTION: 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.
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Authors | Alienor Ragot, Susanna Pietropaolo, Jean Vincent, Pauline Delage, Hongyu Zhang, Bernadette Allinquant, Xavier Leinekugel, André Fischer, Yoon H Cho |
Journal | Brain and behavior
(Brain Behav)
Vol. 5
Issue 9
Pg. e00361
(Sep 2015)
ISSN: 2162-3279 [Electronic] United States |
PMID | 26445700
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Brain-Derived Neurotrophic Factor
- Tubulin
- Hdac6 protein, mouse
- Histone Deacetylase 6
- Histone Deacetylases
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Topics |
- Acetylation
- Animals
- Behavior, Animal
(physiology)
- Brain
(enzymology, metabolism, physiology)
- Brain-Derived Neurotrophic Factor
(metabolism)
- Cognition
(physiology)
- Disease Models, Animal
- Gene Deletion
- Histone Deacetylase 6
- Histone Deacetylases
(genetics, metabolism)
- Huntington Disease
(enzymology, genetics, therapy)
- Male
- Mice
- Mice, Transgenic
- Motor Activity
(physiology)
- Tubulin
(genetics, metabolism)
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