Expression of Reactive Astrocytes in the Deep Cerebellar Nuclei and Inferior Olive of SCA1 Mice

Abstract

Spinocerebellar Ataxia Type 1 (SCA1) is a progressive neurodegenerative disease caused by expansion of over 39 CAG repeats in the gene ATXIN1 (ATXN1). Pathological changes have been primarily associated with the neuronal loss in the cerebellum and brainstem of patients with SCA1. This study focuses on the astrocytes, an important brain cell, in the deep cerebellar nuclei and brainstem, specifically, the inferior olive. (IO). The IO plays a significant role in integrating motor and sensory information to provide feedback between the cerebellum and the spine. Previous research in the lab showed a decreased density of astrocytes in the inferior olive (IO) in mouse models of SCA1. However, this previous study was done at a mid-disease stage after the onset of symptoms and neuronal pathology and little is known about astrocytes in SCA1 DCN. To validate this finding, I quantified the number of astrocytes in the DCN and IO of f-Atxn1146Q/2Q (a new SCA1 mouse model) and their littermate control (wild-type) at an early stage prior to the onset of disease symptoms and neuronal pathology. Quantitative analysis showed a significant increase in the density of astrocytes in the DCN and a decrease in the density of astrocytes in the IO of SCA1 mice compared to wild-type mice. This suggests that astrocytes are altered very early in disease in DCN and IO and may play an important role in SCA1 pathogenesis.