XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent
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.
- Authors:
-
[1];
[1]
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division
- Univ. of Cambridge (United Kingdom). Dept. of Physiology, Development, and Neuroscience
- Univ. of Pittsburgh, PA (United States). Dept. of Chemistry
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1627858
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 13; Journal Issue: 4; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics
Citation Formats
Polyzos, Aris A., Wood, Nigel I., Williams, Paul, Wipf, Peter, Morton, A. Jennifer, and McMurray, Cynthia T. XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent. United States: N. p., 2018.
Web. doi:10.1371/journal.pone.0194580.
Polyzos, Aris A., Wood, Nigel I., Williams, Paul, Wipf, Peter, Morton, A. Jennifer, & McMurray, Cynthia T. XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent. United States. https://doi.org/10.1371/journal.pone.0194580
Polyzos, Aris A., Wood, Nigel I., Williams, Paul, Wipf, Peter, Morton, A. Jennifer, and McMurray, Cynthia T. Mon .
"XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent". United States. https://doi.org/10.1371/journal.pone.0194580. https://www.osti.gov/servlets/purl/1627858.
@article{osti_1627858,
title = {XJB-5-131-mediated improvement in physiology and behaviour of the R6/2 mouse model of Huntington's disease is age- and sex- dependent},
author = {Polyzos, Aris A. and Wood, Nigel I. and Williams, Paul and Wipf, Peter and Morton, A. Jennifer and McMurray, Cynthia T.},
abstractNote = {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.},
doi = {10.1371/journal.pone.0194580},
journal = {PLoS ONE},
number = 4,
volume = 13,
place = {United States},
year = {Mon Apr 09 00:00:00 EDT 2018},
month = {Mon Apr 09 00:00:00 EDT 2018}
}
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Responses to Environmental Enrichment Differ with Sex and Genotype in a Transgenic Mouse Model of Huntington's Disease
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