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Cytoskeleton stability is essential for the integrity of the cerebellum and its motor- and affective-related behaviors.


ABSTRACT: The cerebellum plays a key role in motor tasks, but its involvement in cognition is still being considered. Although there is an association of different psychiatric and cognitive disorders with cerebellar impairments, the lack of time-course studies has hindered the understanding of the involvement of cerebellum in cognitive and non-motor functions. Such association was here studied using the Purkinje Cell Degeneration mutant mouse, a model of selective and progressive cerebellar degeneration that lacks the cytosolic carboxypeptidase 1 (CCP1). The effects of the absence of this enzyme on the cerebellum of mutant mice were analyzed both in vitro and in vivo. These analyses were carried out longitudinally (throughout both the pre-neurodegenerative and neurodegenerative stages) and different motor and non-motor tests were performed. We demonstrate that the lack of CCP1 affects microtubule dynamics and flexibility, defects that contribute to the morphological alterations of the Purkinje cells (PCs), and to progressive cerebellar breakdown. Moreover, this degeneration led not only to motor defects but also to gradual cognitive impairments, directly related to the progression of cellular damage. Our findings confirm the cerebellar implication in non-motor tasks, where the formation of the healthy, typical PCs structure is necessary for normal cognitive and affective behavior.

SUBMITTER: Munoz-Castaneda R 

PROVIDER: S-EPMC5814431 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Cytoskeleton stability is essential for the integrity of the cerebellum and its motor- and affective-related behaviors.

Muñoz-Castañeda Rodrigo R   Díaz David D   Peris Leticia L   Andrieux Annie A   Bosc Christophe C   Muñoz-Castañeda José M JM   Janke Carsten C   Alonso José R JR   Moutin Marie-Jo MJ   Weruaga Eduardo E  

Scientific reports 20180215 1


The cerebellum plays a key role in motor tasks, but its involvement in cognition is still being considered. Although there is an association of different psychiatric and cognitive disorders with cerebellar impairments, the lack of time-course studies has hindered the understanding of the involvement of cerebellum in cognitive and non-motor functions. Such association was here studied using the Purkinje Cell Degeneration mutant mouse, a model of selective and progressive cerebellar degeneration t  ...[more]

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