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Document type
články
články
Document record
Source: BMČ - články
Title
Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model / F. Tichanek, M. Salomova, J. Jedlicka, J. Kuncova, P. Pitule, T. Macanova, Z. Petrankova, Z. Tuma, J. Cendelin,
Author
Tichanek, Filip
Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. f.tichanek@gmail.com. Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. f.tichanek@gmail.com.

Salomova, Martina
Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Jedlicka, Jan
Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. Mitochondrial Laboratory, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Kuncová, Jitka
Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. Mitochondrial Laboratory, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Pitule, Pavel
Laboratory of Tumor Biology, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Macanova, Tereza
Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Petránková, Zuzana
Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Tůma, Zdeněk
Laboratory of Proteomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Cendelín, Jan
Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Cited source
Scientific reports. 2020, roč. 10, č. 1, s. 5418. ISSN: 2045-2322; (OCoLC)732869387.
Date of issue
2020
Language
angličtina
Country
Spojené království
Document type
články
DOI
Pubmed ID
Link
Record number
bmc20028361
Persistent link
MESH descriptor
zvířata
atrofie (metabolismus, patologie)
duševní poruchy (metabolismus, patologie)
mozeček (metabolismus, patologie)
modely nemocí na zvířatech
hipokampus (metabolismus, patologie)
mužské pohlaví
mitochondrie (metabolismus, patologie)
biologické markery (metabolismus)
spinocerebelární ataxie (metabolismus, patologie)
myši
Genre
English 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 (SCA1154Q/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.
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