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Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher Mice

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Abstract

For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for such cases. Nevertheless, there are still severe limitations for routine clinical use. The aim of the work was to assess volume and morphology and functional impact on motor skills of an embryonic cerebellar graft injected in the form of cell suspension in Lurcher mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival period. The grafts survived in the majority of the mice. In both B6CBA and C3H Lurcher mice, most of the grafts were strictly delimited with no tendency to invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells colonized the host’s cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers, the grafts had smaller volume than in their wild-type counterparts. C3H wild-type mice had significantly larger grafts than B6CBA wild-type mice. No positive effect of the transplantation on performance in the rotarod test was observed. The findings suggest that the niche of the Lurcher mutant cerebellum has a negative impact on integration of grafted cells. This factor seems to be limiting for specific functional effects of the transplantation therapy in this mouse model of cerebellar degeneration.

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Acknowledgements

This publication was supported by the Charles University Grant Agency grant 716217, the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic, by the Charles University Research Fund (project number Q39) and student specific research project of the Charles University No. 260 394.

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Authors and Affiliations

  1. Department of Pathophysiology, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655/76, 323 00, Plzen, Czech Republic

    Jan Cendelin, Zdenka Purkartova, Jakub Kubik, Erik Ulbricht & Filip Tichanek

  2. Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655/76, 323 00, Plzen, Czech Republic

    Jan Cendelin & Filip Tichanek

  3. Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Karlovarska 48, 301 66, Plzen, Czech Republic

    Yaroslav Kolinko

  4. Laboratory of Quantitative Histology, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Karlovarska 48, 301 66, Plzen, Czech Republic

    Yaroslav Kolinko

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  1. Jan Cendelin
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Correspondence to Jan Cendelin.

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Cendelin, J., Purkartova, Z., Kubik, J. et al. Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher Mice. Cerebellum 17, 428–437 (2018). https://doi.org/10.1007/s12311-018-0928-3

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