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

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.

• 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)

Chemical References

• Brain-Derived Neurotrophic Factor
• Tubulin
• Hdac6 protein, mouse
• Histone Deacetylase 6
• Histone Deacetylases

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)