Cerebellar extinction lesions can manifest themselves with cerebellar motor and cerebellar cognitive affective syndromes. For investigation of the functions of the cerebellum and the pathogenesis of cerebellar diseases, particularly hereditary neurodegenerative cerebellar ataxias, various cerebellar mutant mice are used. The Lurcher mouse is a model of selective olivocerebellar degeneration with early onset and rapid progress. These mice show both motor deficits as well as cognitive and behavioral changes i.e., pathological phenotype in the functional domains affected in cerebellar patients. Therefore, Lurcher mice might be considered as a tool to investigate the mechanisms of functional impairments caused by cerebellar degenerative diseases. There are, however, limitations due to the particular features of the neurodegenerative process and a lack of possibilities to examine some processes in mice. The main advantage of Lurcher mice would be the expected absence of significant neuropathologies outside the olivocerebellar system that modify the complex behavioral phenotype in less selective models. However, detailed examinations and further thorough validation of the model are needed to verify this assumption.

• Keywords
• Ataxia, Cerebellar Cognitive Affective Syndrome, Cerebellum, Lurcher Mouse, Validity,
• MeSH
• Humans MeSH
• Disease Models, Animal * MeSH
• Cerebellum pathology   physiopathology   MeSH
• Mice, Neurologic Mutants MeSH
• Mice MeSH
• Cerebellar Diseases * genetics   pathology   physiopathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Degenerative effects of nerve tissues are often accompanied by changes in vascularization. In this regard, knowledge about hereditary cerebellar degeneration is limited. In this study, we compared the vascularity of the individual cerebellar components of 3-month-old wild-type mice (n = 8) and Purkinje cell degeneration (pcd) mutant mice, which represent a model of hereditary cerebellar degeneration (n = 8). Systematic random samples of tissue sections were processed, and laminin was immunostained to visualize microvessels. A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in cerebellar layers. Our results in pcd mice revealed a 45% (p < 0.01) reduction in the total volume of the cerebellum, a 28% (p < 0.05) reduction in the total number of vessels and a lower total length, approaching 50% (p < 0.001), compared to the control mice. In pcd mutants, cerebellar degeneration is accompanied by significant reduction in the microvascular network that is proportional to the cerebellar volume reduction therefore does not change density of in the cerebellar gray matter of pcd mice.

• Keywords
• Ataxia, Capillary, Cerebellar degeneration, Microvessels, Pcd mouse, Stereology,
• MeSH
• Microvessels MeSH
• Cerebellum * MeSH
• Mice, Neurologic Mutants MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Purkinje Cells * physiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Edaravone is a mitochondrially targeted drug with a suggested capability to modify the course of diverse neurological diseases. Nevertheless, edaravone has not been tested yet in the context of spinocerebellar ataxia 1 (SCA1), an incurable neurodegenerative disease characterized mainly by cerebellar disorder, with a strong contribution of inflammation and mitochondrial dysfunction. This study aimed to address this gap, exploring the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. SCA1154Q/2Q and healthy SCA12Q/2Q mice were administered either edaravone or saline daily for more than 13 weeks. The functional impairments were assessed via a wide spectrum of behavioral assays reflecting motor and cognitive deficits and behavioral abnormalities. Moreover, we used high-resolution respirometry to explore mitochondrial function, and immunohistochemical and biochemical tools to assess the magnitude of neurodegeneration, inflammation, and neuroplasticity. Data were analyzed using (hierarchical) Bayesian regression models, combined with the methods of multivariate statistics. Our analysis pointed out various previously documented neurological and behavioral deficits of SCA1 mice. However, we did not detect any plausible therapeutic effect of edaravone on either behavioral dysfunctions or other disease hallmarks in SCA1 mice. Thus, our results did not provide support for the therapeutic potential of edaravone in SCA1.

• Keywords
• cerebellum, edaravone, mitochondria, neurodegeneration, spinocerebellar ataxia type 1,
• MeSH
• Bayes Theorem MeSH
• Edaravone pharmacology   therapeutic use   MeSH
• Cognitive Dysfunction * metabolism   MeSH
• Mitochondria MeSH
• Disease Models, Animal MeSH
• Cerebellum metabolism   MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Purkinje Cells MeSH
• Spinocerebellar Ataxias * drug therapy   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Edaravone MeSH