XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent.


Type
Article
Change log
Authors
Wood, Nigel I 
Williams, Paul 
Wipf, Peter 
Morton, A Jennifer 
Abstract

We have reported that the radical scavenger XJB-5-131 attenuates or reverses progression of the disease phenotype in the HdhQ(150/150) mouse, a slow onset model of HD. Here, we tested whether XJB-5-131 has beneficial effects in R6/2 mice, a severe early onset model of HD. We found that XJB-5-131 has beneficial effects in R6/2 mice, by delaying features of the motor and histological phenotype. The impact was sex-dependent, with a stronger effect in male mice. XJB-5-131 treatment improved some locomotor deficits in female R6/2 mice, but the effects were, in general, greater in male mice. Chronic treatment of male R6/2 mice with XJB-5-1-131 reduced weight loss, and improved the motor and temperature regulation deficits, especially in male mice. Treatment with XJB-5-131 had no effect on the lifespan of R6/2 mice. Nevertheless, it significantly slowed somatic expansion at 90 days, and reduced the density of inclusions. Our data show that while treatment with XJB-5-131 had complex effects on the phenotype of R6/2 mice, it produced a number of significant improvements in this severe model of HD.

Description
Keywords
Age Factors, Animals, Behavior, Animal, Body Temperature, Cyclic N-Oxides, Disease Progression, Female, Huntington Disease, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Transgenic, Motor Activity, Phenotype, Sex Factors
Journal Title
PLoS One
Conference Name
Journal ISSN
1932-6203
1932-6203
Volume Title
13
Publisher
Public Library of Science (PLoS)
Sponsorship
CHDI Foundation, Inc (A-4050)