title: Preventive motor training but not progenitor grafting ameliorates cerebellar ataxia and deregulated autophagy in tambaleante mice.
abstract: Treatment options for degenerative cerebellar ataxias are currently very limited. A large fraction of such disorders is represented by hereditary cerebellar ataxias, whose familiar transmission facilitates an early diagnosis and may possibly allow to start preventive treatments before the onset of the neurodegeneration and appearance of first symptoms. In spite of the heterogeneous aetiology, histological alterations of ataxias often include the primary degeneration of the cerebellar cortex caused by Purkinje cells (PCs) loss. Thus, approaches aimed at replacing or preserving PCs could represent promising ways of disease management. In the present study, we compared the efficacy of two different preventive strategies, namely cell replacement and motor training. We used tambaleante (tbl) mice as a model for progressive ataxia caused by selective loss of PCs and evaluated the effectiveness of the preventive transplantation of healthy PCs into early postnatal tbl cerebella, in terms of PC replacement and functional preservation. On the other hand, we investigated the effects of motor training on PC survival, cerebellar circuitry and their behavioral correlates. Our results demonstrate that, despite a good survival rate and integration of grafted PCs, the adopted grafting protocol could not alleviate the ataxic symptoms in tbl mice. Conversely, preventive motor training increases PCs survival with a moderate positive impact on the motor phenotype.
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini, University of Turin, Italy; Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole, 10043 Orbassano, Turin, Italy. Electronic address: elisa.fuca@unito.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fucà
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole, 10043 Orbassano, Turin, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Guglielmotto
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini, University of Turin, Italy; Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole, 10043 Orbassano, Turin, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Boda
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini, University of Turin, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole, 10043 Orbassano, Turin, Italy.
authors.forename: Ketty
authors.initials: K
authors.lastname: Leto
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini, University of Turin, Italy; Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole, 10043 Orbassano, Turin, Italy. Electronic address: annalisa.buffo@unito.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Buffo
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D002470:Cell Survival; D002524:Cerebellar Ataxia / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D005081:Exercise Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D000066829:Neuroprotection; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D013569:Synapses / Q000473:pathology / Q000502:physiology
chemical_list: D049452:Green Fluorescent Proteins
keywords: Mouse; Neurodegeneration; Neuroprotection; Neurotransplantation; Purkinje neurons