Endogenous cerebellar neurogenesis in adult mice with progressive ataxia

摘要: Objective Transplanting exogenous neuronal progenitors to replace damaged neurons in the adult brain following injury or neurodegenerative disorders and achieve functional amelioration is a realistic goal. However, studies so far have rarely taken into consideration preexisting inflammation triggered by disease process that could hamper effectiveness of transplanted cells. Here, we examined fate long-term consequences human cerebellar granule neuron precursors (GNP) cerebellum Harlequin mice, an model progressive degeneration with early-onset microgliosis. Methods Human embryonic stem cell-derived expressing Atoh1, transcription factor key GNP specification, were generated vitro stereotaxically preataxic mice. The histological impact these transplants was followed using immunolabeling Rotarod analysis. Results Although GNPs did not survive beyond few weeks, they proliferation endogenous nestin-positive leptomeninges crossed molecular layer differentiated mature neurons. These phenomena accompanied preservation Purkinje cell layers delayed ataxic changes. In neurosphere generation confirmed enhanced neurogenic potential mice GNPs. Interpretation The contain niche can be stimulated yield from as-yet unidentified population progenitors. transplantation only stimulates this neurogenesis, but, despite potentially hostile environment, leads neuroprotection amelioration.