Resting-state functional MRI reveals altered brain connectivity and its correlation with motor dysfunction in a mouse model of Huntington's disease

Qiang Li, Gang Li, Dan Wu, Hanbing Lu, Zhipeng Hou, Christopher A. Ross, Yihong Yang, Jiangyang Zhang, Wenzhen Duan
2017 Scientific Reports  
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no cure is available currently. Treatment of HD is likely to be most beneficial in the early, possibly premanifestation stage. The challenge is to determine the best time for intervention and evaluate putative efficacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising tool to develop biomarker reflecting early neuronal dysfunction in HD brain, because it can
more » ... ine multiple brain networks without confounding effects of cognitive ability, which makes the restingstate fMRI promising as a translational bridge between preclinical study in animal models and clinical findings in HD patients. In this study, we examined brain regional connectivity and its correlation to brain atrophy, as well as motor function in the 18-week-old N171-82Q HD mice. HD mice exhibited significantly altered functional connectivity in multiple networks. Particularly, the weaker intrastriatum connectivity was positively correlated with striatal atrophy, while striatum-retrosplenial cortex connectivity is negatively correlated with striatal atrophy. The resting-state brain regional connectivity had no significant correlation with motor deficits in HD mice. Our results suggest that altered brain connectivity detected by resting-state fMRI might serve as an early disease biomarker in HD. Huntington disease (HD) is a neurodegenerative disorder resulting from a trinucleotide repeat expansion in the huntingtin gene. To date, proven neuroprotective strategies remain elusive. Part of the problem has been that most of the trials have attempted intervening at a time when the degenerative process is already far advanced and hence when it would be difficult even for the most effective therapy to demonstrate any benefit. Treatment of HD is likely to be most beneficial in the early, possibly pre-manifestation stage. The challenge is to determine the best time for intervention and how to evaluate putative neuroprotection in the absence of clinical symptoms. Therefore noninvasive and objective early biomarkers which are sensitive to changes in neuronal dysfunction during the presymptomatic phase are strongly needed. Multiple neuroimaging modalities have been explored in this regard. Among the biomarkers, the striatal volume is a notably robust marker in HD patients reported by many studies 1-7 as well as in HD mouse models in
doi:10.1038/s41598-017-17026-5 pmid:29196686 pmcid:PMC5711837 fatcat:tjasveek2fcrphlawqz4pjglfu