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Transplantation of Embryonic Cerebellar Grafts Improves Gait Parameters in Ataxic Lurcher Mice

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Abstract

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.

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Acknowledgments

The work was supported by COST grant nos. LD 12057 and LD12056 from the Ministry of Education, Youth, and Sport of the Czech Republic, student specific research project of Charles University, Charles University Grant Agency grant no. 408911, Charles University Research Fund P36, project CZ.1.05/2.1.00/03.0076 from the European Regional Development Fund and was co-financed by the European Social Fund and the state budget of the Czech Republic project no. CZ.1.07/2.3.00/30.0022.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University in Prague, Karlovarska 48, 301 66, Plzen, Czech Republic

    Vaclav Babuska

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

    Zbynek Houdek, Jan Tuma, Zdenka Purkartova, Frantisek Vozeh & Jan Cendelin

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

    Milena Kralickova

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

    Jan Tuma, Milena Kralickova, Frantisek Vozeh & Jan Cendelin

  5. Department of Nutrition and Centre for Research on Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruska 87, 100 00, Praha 10, Czech Republic

    Jana Tumova

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  1. Vaclav Babuska
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Correspondence to Jan Cendelin.

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Babuska, V., Houdek, Z., Tuma, J. et al. Transplantation of Embryonic Cerebellar Grafts Improves Gait Parameters in Ataxic Lurcher Mice. Cerebellum 14, 632–641 (2015). https://doi.org/10.1007/s12311-015-0656-x

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