Identifying Senescence in Tissues Affected by Spinocerebellar Ataxia Type 7

Abstract

Background: Spinocerebellar Ataxia Type 7 (SCA7) is an age-related neurodegenerative disease caused by a trinucleotide CAG repeat. SCA7 predominantly causes a loss of photoreceptors of the retina and Purkinje cells of the cerebellum, but severe forms also cause renal and cardiac irregularities. Previous reports have shown that SCA7 results in increased susceptibility to DNA damage. Increased DNA damage can lead to an accumulation of senescent cells, which is known to contribute to other age-related diseases. Hypothesis: SCA7 causes an accumulation of senescent cells in affected tissues over the course of disease. Methods: A 266 CAG SCA7 mouse model was evaluated for renal and cardiac dysfunction in addition to previously described metabolic and neurologic problems. Senescence was evaluated in the kidneys and cerebellum of these mice via RT-qPCR for the cell cycle inhibitors p16 and p21 and staining for SA-ßgal Results: Senescent cells accumulate in the kidneys of these mice throughout the course of disease. The Purkinje layer in the cerebellum of the SCA7 mice display increased SA-ßgal staining, potentially displaying a senescent-like phenotype.