Embryonic Cerebellar Graft Morphology Differs in Two Mouse Models of Cerebellar Degeneration

Purkartová, Zdeňka; Tichánek, Filip; Kolinko, Yaroslav; Cendelín, Jan

doi:10.1007/s12311-019-01067-9

Cited by 8 publications

(1 citation statement)

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“…The brains were subsequently removed and left in PFA for 2 hours and then in sucrose (15, 20, 30%) for 2 days. Finally, they were weighed and frozen at −80 °C; as described in detail elsewhere 70,71 . They were then cut into 40 µm wide frontal slices and stained using Cresyl Violet (Nissl staining) or immunofluorescent methods.…”

Section: Methodsmentioning

confidence: 99%

Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model

Tichánek

Šalomová

Jedlička

et al. 2020

Sci Rep

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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. Spinocerebellar ataxia type 1 (SCA1) is a lethal dominantly-inherited neurodegenerative disease, caused by CAG repeat expansion (> 40 CAG repeats) in the ataxin-1 encoding gene (ATXN1) 1. This mutation results in ataxin-1 protein toxicity and aggregation which leads, in particular, to cerebellar and brainstem degeneration 2 , although ATXN1 is widely expressed throughout the brain 1. SCA1 symptoms usually appear in early middle-age and include motor incoordination and gait deficits followed by muscular and swallowing problems in the later stages of the disease 3. However, in a similar way to other types of spinocerebellar ataxias (SCAs), over 50% of patients also demonstrate neuropsychiatric issues 4-7 including cognitive impairments, anxiety, apathy and depression 7-9. Interestingly, in contrast to progressive ataxia, the psychiatric impairments tend to remain relatively stable over time 8. Although they are often overlooked, they profoundly impact the quality of life and health outcomes of patients with SCA1 and related diseases 9. However, the question of whether these psychiatric impairments are causally linked to SCA1 neuropathology, or if they represent an emotional response to SCA1 diagnosis and subsequent physical disability, remains controversial 9 .

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Section: Methodsmentioning

confidence: 99%