Graft-induced restoration of function in hereditary cerebellar ataxia.
Fetal cerebellar cell suspensions, prepared from wild-type (+/+) mice, were implanted bilaterally into the cerebellum of Purkinje cell degeneration' (pcd) mutant mice, a model of adult-onset recessively inherited cerebellar ataxia, to study the functional effects of the grafts on motor coordination and fatigue resistance in a rotating rod treadmill paradigm. The viability of transplanted Purkinje cells was verified with immunocytochemistry for calbindin-D28k and for glutamate receptor 2/3 subunits and with in situ hybridisation histochemistry for insulin-like growth factor I mRNA, biochemical markers normally expressed by Purkinje cells in the cerebellum. Sham injections of vehicle did not appreciably modify the performance of pcd mutants in the rota-rod tests. On the other hand, bilateral cerebellar grafts led to a 3.5-fold increase in the time period that recipient pcd mice were able to stay on the rotating drum based on the comparison of mean scores (of three trials) or a 5.5-fold increase based on the comparison of maximum scores (of the three trials). These findings provide evidence for a motor enhancement in the pcd mouse model of hereditary cerebellar ataxia following intracerebellar transplantation of primordial Purkinje cells.
Triarhou
L C
LC
Department of Pathology, Indiana University School of Medicine, Indianapolis 46202, USA.
Zhang
W
W
Lee
W H
WH
D000818:Animals; D017690:Cell Transplantation; D002529:Cerebellar Nuclei / Q000601:surgery; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology; D016332:Fetal Tissue Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D011597:Psychomotor Performance / Q000502:physiology*; D013132:Spinocerebellar Degenerations / Q000601:surgery*