Toxin-produced Purkinje cell death: a model for neural stem cell transplantation studies

Purkinje cell loss is the hallmark of the cerebellar ataxias. Here the fungal neurotoxin Penitrem A was used to create partially Purkinje-cell-deficient cerebella in neonate and young adult rats suitable for use in neural stem cell transplantation studies. I.p. administration of Penitrem A to P3, P6 and 11-week old rats caused noticeable tremor in all treated animals that lasted between 1 and 3 days and was more immediate in the rat pups than in the 11-week old rats. Quantification of cresyl violet stained sections showed that Purkinje cells were preferentially lost in the cerebellar vermis and specifically in folia VI to IX (P<0.001-0.05). No change occurred in Purkinje cell number in folia I-III and folium X. These results were confirmed by the loss of calbindin binding cells in the Purkinje cell layer and the appearance of enlarged vacuolated mitochondria. The results of the present study show that the Penitrem A can remove Purkinje cells in the immature rat cerebellum and thus provide a potential model to study the micro-environmental cues in vivo for the differentiation of Purkinje cells from transplanted and/or intrinsic neural stem cells.