Correlations Between Mutant Huntingtin Aggregates and Behavioral Changes in R6/1 Mice
JHD. 2020-02-10; 9(1): 33-45
DOI: 10.3233/jhd-190352
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1. J Huntingtons Dis. 2020;9(1):33-45. doi: 10.3233/JHD-190352.
Correlations Between Mutant Huntingtin Aggregates and Behavioral Changes in R6/1
Mice.
Cabanas M(1)(2), Piquemal M(1)(2), Pistono C(1)(2), Arnaud S(1)(2), Rakesh
D(1)(2), Poinama E(1)(2), Guillou JL(1)(2), Garret M(1)(2), Cho YH(1)(2).
Author information:
(1)Institute of Cognitive and Integrative Neuroscience of Aquitaine, CNRS UMR
5287, Pessac Cedex, France.
(2)Institute of Cognitive and Integrative Neuroscience of Aquitaine, University
of Bordeaux, Bordeaux Cedex, France.
BACKGROUND: Huntington’s disease (HD) is a neurodegenerative disorder caused by
the expansion of the trinucleotide CAG in the HD gene. While the presence of
nuclear aggregates of mutant huntingtin (mHtt) in neurons is a hallmark of HD,
the reason behind its toxicity remains elusive.
OBJECTIVE: The present study was conducted to assess a correlation between the
number of mHtt aggregates and the severity of HD symptoms in R6/1 mice.
METHODS: We investigated correlations between behavioral deficits and the level
of nuclear mHtt aggregates in different neuroanatomical regions in 3-month-old
R6/1 mice, the age at which a large variability of symptom severity between
animals has been observed.
RESULTS: R6/1 mice were deficient in instinctive and anxiety related behaviors as
well as long-term memory capabilities. Significant differences were also found
between the sexes; female transgenic mice displayed less severe deficits than
males. While the level of mHtt aggregates was correlated with the severity of HD
phenotypes in most regions of interest, an opposite relationship also was found
for some other regions examined.
CONCLUSIONS: The obtained results suggest harmful and region-specific roles of
mHtt aggregates in HD symptoms.
DOI: 10.3233/JHD-190352
PMID: 31868674 [Indexed for MEDLINE]