Ataxin-1 in cognition and mood

Abstract

Ataxin-1 (ATXN1), the gene mutated in spinocerebellar ataxia type 1 (SCA1), may affect cognition and mood, but much remains unknown, including which brain areas are responsible, whether ATXN1 affects mood in mice, and the mechanisms of these effects. To answer these questions, we characterized cognition and mood in several ATXN1 mutant mouse lines: Atxn1+/- and Atxn1-/- mice to compare 50% and 100% loss of ATXN1; Atxn1154Q/2Q and Atxn178Q/2Q mice to compare SCA1-like polyglutamine expansions of different lengths; and Purkinje cell specific Pcp2-ATXN1[82Q] mice to determine the cerebellar contribution. Atxn1-/- and Atxn1154Q/2Q mice showed cognitive deficits. Reduced hippocampal neurogenesis in Atxn1-/- mice may explain this. Cognition was not affected in Atxn1+/-, Atxn178Q/2Q, or Pcp2-ATXN1[82Q] mice. We also observed mood abnormalities not consistent with depression or anxiety. These results provide a foundation for further research into the function of ataxin-1 and the potential side effects of reducing ataxin-1 levels to treat SCA1.