Embryonic Cerebellar Graft Morphology Differs in Two Mouse Models of Cerebellar Degeneration
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Cerebellar diseases causing substantial cell loss often lead to severe functional deficits and restoration of cerebellar function is difficult. Neurotransplantation therapy could become a hopeful method, but there are still many limitations and unknown aspects. Studies in a variety of cerebellar mutant mice reflecting heterogeneity of human cerebellar degenerations show promising results as well as new problems and questions to be answered. The aim of this work was to compare the development of embryonic cerebellar grafts in adult B6CBA Lurcher and B6.BR pcd mutant mice and strain-matched healthy wild type mice. Performance in the rotarod test, graft survival, structure, and volume was examined 2 months after the transplantation or sham-operation. The grafts survived in most of the mice of all types. In both B6CBA and B6.BR wild type mice and in pcd mice, colonization of the host’s cerebellum was a common finding, while in Lurcher mice, the grafts showed a low tendency to infiltrate the host’s cerebellar tissue. There were no significant differences in graft volume between mutant and wild type mice. Nevertheless, B6CBA mice had smaller grafts than their B6.BR counterparts. The transplantation did not improve the performance in the rotarod test. The study showed marked differences in graft integration into the host’s cerebellum in two types of cerebellar mutants, suggesting disease-specific factors influencing graft fate.
KeywordsAtaxia Cerebellar degeneration Lurcher mouse Neurotransplantation Pcd mouse
This publication was supported by the Charles University Grant Agency grant 716217; the National Sustainability Program I (NPU I) No. LO1503 provided by the Ministry of Education, Youth and Sports of the Czech Republic; the Charles University Research Fund (project number Q39); and the student-specific research project of Charles University No. 260 394.
Compliance with Ethical Standards
All experimental procedures were performed in compliance with EU guidelines for scientific experimentation on animals and with the permission of the Ethical Commission of the Faculty of Medicine in Pilsen.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 15.Wetts R, Herrup K. Interaction of granule, Purkinje and inferior olivary neurons in lurcher chimaeric mice. I. Qualitative studies. J Embryol Exp Morpholog. 1982;68:87–98.Google Scholar
- 32.Triarhou LC. Biological clues on neuronal degeneration based on theoretical fits of decay patterns: towards a mathematical neuropathology. Folia Neuropathol. 2010;48:3–10.Google Scholar
- 50.R Core Team. R 2017. A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org/.
- 53.Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995;57:289–300.Google Scholar