Correlations Between Mutant Huntingtin Aggregates and Behavioral Changes in R6/1 Mice
Magali Cabanas1,2, Marion Piquemal1,2, Cristiana Pistono1,2
1Institute of Cognitive and Integrative Neuroscience of Aquitaine, CNRS UMR 5287, Pessac Cedex, France.
Journal of Huntington'S Disease
|December 24, 2019
Summary
Huntington's disease (HD) involves mutant huntingtin (mHtt) aggregates in neurons. This study in R6/1 mice shows mHtt aggregate levels correlate with HD symptom severity, but this relationship varies by brain region.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Huntington's disease (HD) is a neurodegenerative disorder.
- Caused by CAG trinucleotide expansion in the HD gene.
- Nuclear aggregates of mutant huntingtin (mHtt) are a hallmark, but their toxicity mechanism is unclear.
Purpose of the Study:
- To assess the correlation between mHtt aggregate load and HD symptom severity in R6/1 mice.
- To investigate regional differences in this correlation.
Main Methods:
- Utilized 3-month-old R6/1 mice, an age exhibiting variable symptom severity.
- Examined correlations between behavioral deficits and nuclear mHtt aggregate levels in specific neuroanatomical regions.
- Assessed instinctive, anxiety-related, and long-term memory behaviors.
Main Results:
- R6/1 mice showed deficits in instinctive, anxiety-related, and long-term memory behaviors.
- Female mice exhibited less severe deficits than males.
- mHtt aggregate levels correlated with HD phenotypes in most regions, but an inverse correlation was observed in others.
Conclusions:
- mHtt aggregates play a harmful role in HD symptoms.
- The impact of mHtt aggregates is region-specific within the brain.
