Investigating the Role of Chronic Exercise and Autophagy in a Poly(GR) Mouse Model of Frontotemporal Dementia
Faculty AdvisorFen-Biao Gao
UMass Chan AffiliationsNeurology
Document TypeMaster's Thesis
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AbstractUnderstanding how exercise can attenuate social and cellular deficits seen in frontotemporal dementia (FTD) could provide a unique insight and potential for new therapeutic approaches to help patients suffering from FTD and other devastating FTD associated diseases such as Amyotrophic Lateral Sclerosis (ALS). This project helped study the effect of chronic exercise in a poly(GR)-specific mouse model of FTD, highlighting the specific response exercise has on autophagy and poly(GR) toxicity in this experimental system. The goal of this work was to identify the amount/type of exercise that would be most beneficial to reduce poly(GR) load or other neurotoxicity indicators; as well as, identifying the mechanism underlying autophagy disfunction with GR80 overexpression, and if exercise could also alleviate this disruption. Additionally, to compliment the cortical neuron FTD specific mouse model being used to investigate exercise, we also wanted to make a motor neuron mouse model to better understand poly(GR)’s contribution specifically to ALS. In doing this we used Homeobox Protein 9 (HB9) as a promoter due to its lack of expression in sensory and interneurons, in hopes to study motor neurons only. With a understanding of how poly(GR) impacts both FTD and ALS respectively we can better understand the disease pathology progression and hopefully uncover novel ways to intervene, treat, or prevent these disease more effectively.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52781
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