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- W3013100382 abstract "Abstract Spinocerebellar ataxia 1 (SCA1) is a devastating neurodegenerative disease associated with cerebellar degeneration and motor deficits. However, many patients also exhibit neuropsychiatric impairments such as depression and apathy; nevertheless, the existence of a causal link between the psychiatric symptoms and SCA1 neuropathology remains controversial. This study aimed to explore behavioral deficits in a knock-in mouse SCA1 (SCA1 154Q/2Q ) model and to identify the underlying neuropathology. We found that the SCA1 mice exhibit previously undescribed behavioral impairments such as increased anxiety- and depressive-like behavior and reduced prepulse inhibition and cognitive flexibility. Surprisingly, non-motor deficits characterize the early SCA1 stage in mice better than does ataxia. Moreover, the SCA1 mice exhibit significant hippocampal atrophy with decreased plasticity-related markers and markedly impaired neurogenesis. Interestingly, the hippocampal atrophy commences earlier than the cerebellar degeneration and directly reflects the individual severity of some of the behavioral deficits. Finally, mitochondrial respirometry suggests profound mitochondrial dysfunction in the hippocampus, but not in the cerebellum of the young SCA1 mice. These findings imply the essential role of hippocampal impairments, associated with profound mitochondrial dysfunction, in SCA1 behavioral deficits. Moreover, they underline the view of SCA1 as a complex neurodegenerative disease and suggest new avenues in the search for novel SCA1 therapies." @default.
- W3013100382 created "2020-04-03" @default.
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- W3013100382 date "2020-03-25" @default.
- W3013100382 modified "2023-10-12" @default.
- W3013100382 title "Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model" @default.
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- W3013100382 doi "https://doi.org/10.1038/s41598-020-62308-0" @default.
- W3013100382 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7096488" @default.
- W3013100382 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32214165" @default.
- W3013100382 hasPublicationYear "2020" @default.
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