1. Altered anterograde axonal transport of mitochondria in cultured striatal neurons of a knock-in mouse model of Huntington's disease.
- Author
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Wu, Chao, Yin, Haoran, Fu, Songdi, Yoo, Hanna, Zhang, Min, and Park, Hyokeun
- Subjects
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HUNTINGTON disease , *AXONAL transport , *DOPAMINERGIC neurons , *LABORATORY mice , *ANIMAL disease models , *MITOCHONDRIA , *DOPAMINE receptors - Abstract
Huntington's disease (HD) is a progressive genetic neurodegenerative disease caused by an abnormal expansion of a cytosine-adenine-guanine trinucleotide repeat in the huntingtin gene. One pathological feature of HD is neuronal loss in the striatum. Despite many efforts, mechanisms underlying neuronal loss in HD striatum remain elusive. It was suggested that the mutant huntingtin protein interacts mitochondrial proteins and causes mitochondrial dysfunction in striatal neurons. However, whether axonal transport of mitochondria is altered in HD striatal neurons remains controversial. Here, we examined axonal transport of single mitochondria labelled with Mito-DsRed2 in cultured striatal neurons of zQ175 knock-in mice (a knock-in mouse model of HD). We observed decreased anterograde axonal transport of proximal mitochondria in HD striatal neurons compared with wild-type (WT) striatal neurons. Decreased anterograde transport in HD striatal neurons was prevented by overexpressing mitochondrial Rho GTPase 1 (Miro1). Our results offer a new insight into mechanisms underlying neuronal loss in the striatum in HD. • Cultured striatal neurons were mainly MSNs that are the most vulnerable neurons in HD. • Anterograde axonal transport of proximal mitochondria was altered in HD striatal neurons. • Overexpressing Miro1 prevented altered mitochondrial transport in HD striatal neurons. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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