Laurel Schuck

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease that is caused by an abnormal expansion of a glutamine-encoding CAG repeat in the ATXN1 gene. Patients with SCA1 experience difficulties with coordination and balance as well as speaking and even swallowing as the disease progresses in severity. This research aimed to investigate the role of gliosis in late stage SCA1 using a knock in mouse model of SCA1 and genetic modification of inflammatory signaling in astrocytes. To modify gliosis, we used a Tamoxifen inducible Cre-Lox system to prevent activation of the proinflammatory gene NF-KB. Using qPCR, I analyzed the expression of genes indicating astrogliosis as well as genes previously shown to correlate with Purkinje cell health. I worked with tissue from the cerebellum, medulla, hippocampus, and cortex of the mouse models. I found that inhibiting astrogliosis showed beneficial effects in the cerebellum and cortex, potentially detrimental effects in the medulla, and negligible effects in the hippocampus. Further, despite the common assumption that Tamoxifen does not affect SCA1 and gliosis, analysis showed a trend of Tamoxifen injection decreasing glial response in the cerebellum as well as rescuing Purkinje neurons from damage. However, these results are to be treated as inconclusive due to the small sample size of mice utilized in my research.