title: Early activation of microglia and astrocytes in mouse models of spinocerebellar ataxia type 1.
abstract: Spinocerebellar ataxia type 1 (SCA1) is an incurable, dominantly inherited neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat expansion in the protein ataxin-1 (ATXN1). While analysis of human autopsy material indicates significant glial pathology in SCA1, previous research has focused on characterizing neuronal dysfunction. In this study, we characterized astrocytic and microglial response in SCA1 using a comprehensive array of mouse models. We have discovered that astrocytes and microglia are activated very early in SCA1 pathogenesis even when mutant ATXN1 expression was limited to Purkinje neurons. Glial activation occurred in the absence of neuronal death, suggesting that glial activation results from signals emanating from dysfunctional neurons. Finally, in all different models examined glial activation closely correlated with disease progression, supporting the development of glial-based biomarkers to follow disease progression.
authors.affiliation: Department of Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, United States. Electronic address: mcvetano@umn.edu.
authors.forename: M
authors.initials: M
authors.lastname: Cvetanovic
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, United States.
authors.forename: M
authors.initials: M
authors.lastname: Ingram
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, United States.
authors.forename: H
authors.initials: H
authors.lastname: Orr
authors.affiliation: Neurology and Department of Cell and Molecular Biology, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, United States.
authors.forename: P
authors.initials: P
authors.lastname: Opal
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D000067696:Ataxin-1 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D055879:Gene Knock-In Techniques; D006801:Humans; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D009154:Mutation; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology; D012720:Severity of Illness Index; D020754:Spinocerebellar Ataxias / Q000473:pathology / Q000503:physiopathology*
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D016207:Cytokines
keywords: SCA1; astrocytes; glia; microglia; neurodegeneration; spinocerebellar ataxia type 1