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Sci Rep. 2018 Feb 15;8(1):3072. doi: 10.1038/s41598-018-21470-2.

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

Author information

1
Laboratory of Neural Plasticity and Neurorepair. Institute for Neurosciences of Castile and Leon (INCyL), University of Salamanca, E-37007, Salamanca, Spain.
2
Institute for Biomedical Research of Salamanca (IBSAL), E-37007, Salamanca, Spain.
3
Inserm, U1216, F-38000, Grenoble, France.
4
Université Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000, Grenoble, France.
5
CEA, BIG-GPC, F-38000, Grenoble, France.
6
Physics Department, Aeronautics Engineering School, Polytechnic University of Madrid, E-28040, Madrid, Spain.
7
Institut Curie, F-91405, Orsay, France.
8
Paris Sciences et Lettres Research University, F-75005, Paris, France.
9
Centre National de la Recherche Scientifique, UMR3348, F-91405, Orsay, France.
10
Institute for Higher Research, University of Tarapaca, Arica, Chile.
11
Laboratory of Neural Plasticity and Neurorepair. Institute for Neurosciences of Castile and Leon (INCyL), University of Salamanca, E-37007, Salamanca, Spain. ewp@usal.es.
12
Institute for Biomedical Research of Salamanca (IBSAL), E-37007, Salamanca, Spain. ewp@usal.es.

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.

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