THESIS
2017
xiii, 60 pages : illustrations (some color) ; 30 cm
Abstract
Huntington’s disease (HD) is an autosomal genetic neurodegenerative disorder caused by the
expansion of CAG in the huntingtin gene. Mutated Huntingtin proteins induce neuronal death
in cortex and striatum regions followed by other brain regions. Mitochondrial and autophagy
dysfunctions are thought to be a key pathogenic mechanism of HD. However, the neuritic
transport of mitochondria and autophagosomes in HD primary neurons is not clearly
understood yet. Our data indicated that the spatial distributions of mitochondria were affected
in HD/GFP-mt crossed mice. Furthermore, the real-time live-cell imaging data showed that
the percentage of moving mitochondria via neurites significantly decreased in HD neurons in
an age dependent manner, and also mitochondrial transport behavior wa...[
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Huntington’s disease (HD) is an autosomal genetic neurodegenerative disorder caused by the
expansion of CAG in the huntingtin gene. Mutated Huntingtin proteins induce neuronal death
in cortex and striatum regions followed by other brain regions. Mitochondrial and autophagy
dysfunctions are thought to be a key pathogenic mechanism of HD. However, the neuritic
transport of mitochondria and autophagosomes in HD primary neurons is not clearly
understood yet. Our data indicated that the spatial distributions of mitochondria were affected
in HD/GFP-mt crossed mice. Furthermore, the real-time live-cell imaging data showed that
the percentage of moving mitochondria via neurites significantly decreased in HD neurons in
an age dependent manner, and also mitochondrial transport behavior was spatially and
temporally regulated in both wild type WT and HD of primary cortical and striatal neurons.
Mitochondria in the proximal, middle and distal region had different transport patterns in
different neuronal development stages, and they were distinctively affected in the primary
cortical and striatal neurons of HD. Additionally, more small moving mitochondria, whose
transport behavior was significantly different from large moving mitochondria, existed in HD
with an age-dependent manner, indicating that mitochondria were under more stress
condition in HD. The autophagosome data showed that neuritic swelling existed in some of
HD cortical neurons at basal level. Moving autophagosomes had lower speed in the transition
stage from young stage to mature stage in HD cortical neurons, while striatal moving
autopahgosomes showed higher speed in the same stage in HD. Also, the moving
autophagosomes’ transport was differently regulated in different neuronal stages and regions
at basal level. Taken together, mitochondrial and autophagosomes’ transport were altered in
both striatal and cortical neurons of HD, which implied mitochondria and autophagosomes as
potential therapeutic targets of HD.
Key words: Huntington’s disease, mitochondria, autophagosomes, real-time live-cell imaging
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