Analysis of Differentially Expressed Genes in the Deep Cerebellar Nuclei of 154Q Spinocerebellar Ataxia Type 1 Mouse Models
Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disorder characterized by glutamine (Q) repeats on the ATAXIN1 (ATXN1) gene. Symptoms include ataxia, cognitive impairment, and nystagmus. Deep cerebellar nuclei (DCN) are understudied in SCA1 and no research exists on how gene expression is affected in the DCN. The DCN consist of the fastigial, interposed, and dentate nuclei and are the output of the cerebellum to other brain regions. This study analyzed RNA-sequencing data, comparing 154Q and wild type mice, and conducted qPCR on several genes found to be differentially expressed in the DCN: CRHR1, IL20RB, PLEKHG4, OAS1G, CST7, and ACTA1. ACTA1 was inconclusive, whereas CRHR1, IL20RB, and PLEKHG4 were all downregulated 154Q mice compared to wild type mice. OAS1G and CST7 were all upregulated in 154Q mice compared to wild type mice. These differentially expressed genes and their pathways are not well understood in the DCN and could have their pathways elucidated for future pharmacological treatments of SCA1. Understanding how these genes function in the DCN could also provide a causal relationship for SCA1 symptoms.