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SCA2 transgenic mice are thought to be a useful model of human spinocerebellar ataxia type 2. There is no effective therapy for cerebellar degenerative disorders, therefore neurotransplantation could offer hope. The aim of this work was to assess the survival and morphology of embryonic cerebellar grafts transplanted into the cerebellum of adult SCA2 mice. Four month-old homozygous SCA2 and negative control mice were treated with bilateral intracerebellar injections of an enhanced green fluorescent protein-positive embryonic cerebellar cell suspension. Graft survival and morphology were examined three months later. Graft-derived Purkinje cells and the presence of astrocytes in the graft were detected immunohistochemically. Nissl and hematoxylin-eosin techniques were used to visualize the histological structure of the graft and surrounding host tissue. Grafts survived in all experimental mice; no differences in graft structure, between SCA2 homozygous and negative mice, were found. The grafts contained numerous Purkinje cells but long distance graft-to-host axonal connections to the deep cerebellar nuclei were rarely seen. Relatively few astrocytes were found in the center of the graft. No signs of inflammation or tissue destruction were seen in the area around the grafts. Despite good graft survival and the presence of graft-derived Purkinje cells, the structure of the graft did not seem to promise any significant specific functional effects. We have shown that the graft is available for long-term experiments. Nevertheless, it would be beneficial to search for ways of enhancement of connections between the graft and host., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Lurcher mutant mice represent a natural model of olivocerebellar degeneration. They serve as a tool to study pathogenesis, the functional impact of the degeneration as well as therapeutic approaches. Wild type littermates are used as healthy controls. Neurotransplantation may be a promising method of therapy for neurodegenerative diseases. The aim of this work was to compare the long-term survival rate of the solid embryonic cerebellar graft in adult Lurcher mutant and wild type mice of the B6CBA strain and to assess the fundamental structural features of the graft. The graft was obtained from 12-day-old GFP mouse embryos. The brains of host mice were examined histologically 6 months after the transplantation. The graft was identified according to its GFP fluorescence. The graft presence and structure was assessed. The graft survived in all 14 Lurcher mice and in 12 of the 14 wild type mice. Cell migration and fibre sprouting from the graft were poor. No marked differences in the graft morphology between Lurcher mutant and wild type mice were found. The graft survival and appearance were similar to those after a shorter period described in a previous study. This suggests that during the 6 months, no intensive or commonly occurring processes changing the graft had proceeded and that the Lurcher mutant cerebellum niche had no strong influence over the fate of the solid cerebellar graft., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Normal cerebellar tissue, obtained from 15-day-old CBA/JNCij mouse embryos, was transplanted into the cerebellum of 4-week-old weaver mice. At the 6th week after the transplantation, the grafted tissue was distinguishable from the host cerebellum, developing a trilaminar organization. The formation of synapses by the implanted granule cells was analyzed immunohistochemically with antiserum against synaptic vesicle protein, Synapsin I. Some areas in the host cerebellum as well as in the grafted tissue were intensely stained by anti-Synapsin I serum, suggesting that the implanted granule cells make synaptic contacts with the neuronal cells.

Transplantation of embryonic day 11 cerebellar anlage to the anterior eye chamber of wildtype recipient mice was used to investigate the intrinsic character of the cerebellar mutation staggerer. One phenotypic expression of the staggerer gene in vivo is a postnatal degeneration of cerebellar granule cells. After 43 days of in oculo development cerebellar buds from homozygous staggerer embryos similarly develop into nervous tissues lacking granule cells. On the other hand, transplants of wildtype cerebellar anlagen contain a large population of granule cells. Both the staggerer and wildtype cerebellar transplants had a survival of large neurons, characteristic of Purkinje, Golgi and deep nuclei cells.