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.

• Klíčová slova
• Ataxia, Cerebellar Cognitive Affective Syndrome, Cerebellum, Lurcher Mouse, Validity,
• MeSH
• cerebelární ataxie genetika   patofyziologie   patologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• mozeček patologie   patofyziologie   MeSH
• myši - mutanty neurologické MeSH
• myši MeSH
• nemoci mozečku * patologie   patofyziologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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.

• Klíčová slova
• cerebellum, edaravone, mitochondria, neurodegeneration, spinocerebellar ataxia type 1,
• MeSH
• Bayesova věta MeSH
• edaravon farmakologie   terapeutické užití   MeSH
• kognitivní dysfunkce * metabolismus   MeSH
• mitochondrie MeSH
• modely nemocí na zvířatech MeSH
• mozeček metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• Purkyňovy buňky MeSH
• spinocerebelární ataxie * farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• edaravon MeSH

It has been shown that Lurcher mutant mice have significantly altered motor abilities, regarding their motor coordination and muscular strength because of olivorecebellar degeneration. We assessed the response of the cross-sectional geometry and lacuno-canalicular network properties of the tibial mid-diaphyseal cortical bone to motor differences between Lurcher and wild-type (WT) male mice from the B6CBA strain. The first data set used in the cross-sectional geometry analysis consists of 16 mice of 4 months of age and 32 mice of 9 months of age. The second data set used in the lacunar-canalicular network analysis consists of 10 mice of 4 months of age. We compared two cross-sectional geometry and four lacunar-canalicular properties by I-region using the maximum and minimum second moment of area and anatomical orientation as well as H-regions using histological differences within a cross section. We identified inconsistent differences in the studied cross-sectional geometry properties between Lurcher and WT mice. The biggest significant difference between Lurcher and WT mice is found in the number of canaliculi, whereas in the other studied properties are only limited. Lurcher mice exhibit an increased number of canaliculi (p < 0.01) in all studied regions compared with the WT controls. The number of canaliculi is also negatively correlated with the distance from the centroid in the Lurcher and positively correlated in the WT mice. When the Lurcher and WT sample is pooled, the number of canaliculi and lacunar volume is increased in the posterior Imax region, and in addition, midcortical H-region exhibit lower number of canaliculi, lacuna to lacuna distance and increased lacunar volume. Our results indicate, that the importance of precise sample selection within cross sections in future studies is highlighted because of the histological heterogeneity of lacunar-canalicular network properties within the I-region and H-region in the mouse cortical bone.

• MeSH
• biomechanika MeSH
• bludiště - učení * MeSH
• diafýzy MeSH
• druhová specificita MeSH
• konfokální mikroskopie MeSH
• křížení genetické MeSH
• mutace MeSH
• myši - mutanty neurologické * MeSH
• myši MeSH
• počítačové zpracování obrazu MeSH
• tibie fyziologie   MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hereditary cerebellar ataxias are severe diseases for which therapy is currently not sufficiently effective. One of the possible therapeutic approaches could be neurotransplantation. Lurcher mutant mice are a natural model of olivocerebellar degeneration representing a tool to investigate its pathogenesis as well as experimental therapies for hereditary cerebellar ataxias. The effect of intracerebellar transplantation of embryonic cerebellar solid tissue or cell suspension on motor performance in adult Lurcher mutant and healthy wild-type mice was studied. Brain-derived neurotrophic factor level was measured in the graft and adult cerebellar tissue. Gait analysis and rotarod, horizontal wire, and wooden beam tests were carried out 2 or 6 months after the transplantation. Higher level of the brain-derived neurotrophic factor was found in the Lurcher cerebellum than in the embryonic and adult wild-type tissue. A mild improvement of gait parameters was found in graft-treated Lurcher mice. The effect was more marked in cell suspension grafts than in solid transplants and after the longer period than after the short one. Lurcher mice treated with cell suspension and examined 6 months later had a longer hind paw stride (4.11 vs. 3.73 mm, P < 0.05) and higher swing speed for both forepaws (52.46 vs. 32.79 cm/s, P < 0.01) and hind paws (63.46 vs. 43.67 cm/s, P < 0.001) than controls. On the other hand, classical motor tests were not capable of detecting clearly the change in the motor performance. No strong long-lasting negative effect of the transplantation was seen in wild-type mice, suggesting that the treatment has no harmful impact on the healthy cerebellum.

• Klíčová slova
• Ataxia, Cerebellar transplantation, Gait analysis, Lurcher, Olivocerebellar degeneration,
• MeSH
• časové faktory MeSH
• chůze (způsob) MeSH
• metoda rotující tyčky MeSH
• mozeček embryologie   metabolismus   transplantace   MeSH
• mozkový neurotrofický faktor metabolismus   MeSH
• multisystémová atrofie patofyziologie   terapie   MeSH
• myši - mutanty neurologické MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• pohybová aktivita MeSH
• spinocerebelární degenerace patofyziologie   terapie   MeSH
• transplantace fetální tkáně metody   MeSH
• transplantace mozkové tkáně metody   MeSH
• výsledek terapie MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• enhanced green fluorescent protein MeSH Prohlížeč
• mozkový neurotrofický faktor MeSH
• zelené fluorescenční proteiny MeSH