• neurogenesi
• ippocampo
• malattia prionica

Neurogenesis is impaired during chronic progressive neurodegenerative diseases, with the potential to replace damaged neurons at lesion sites. These findings support the need for a better understanding of injury-induced neurogenesis in the adult brain undergoing neurodegeneration and suggest the potential of directing neural precursor regulation as a strategy for brain repair. Among the existing experimental models of neurodegeneration, prion disease models present many features in common with diseases such as Alzheimer’s or Parkinson’s and is an ideal tractable laboratory model to study chronic progressive neurodegenerative diseases.
In the present work, using the ME7 murine model of prion disease, we studied the dynamics and regulation of neurogenesis since this would provide a basis for the therapeutical manipulation of neurogenesis which would impact both behaviour and pathology. Our results provide insights into the dynamics of hippocampal cell death and the generation of neural precursor cells and new neurons in the dentate gyrus (DG) region. Using retroviral vectors to label and trace proliferating cells, we found significant changes in the maturation and integration of newly generated neurons within the DG. In addition, using conditional ablation of the prion protein (PrP) in neurons we also investigated the role of differentiated neurons in the regulation of neurogenesis during the course of prion disease. Finally, we studied neurogenesis in hippocampi from variant Creutzfeldt-Jacob’s disease (vCJD) and Alzheimer’s disease (AD) patients, showing similarities with the results obtained in the murine model of prion disease.
The present results describe for the first time the regulation of neurogenesis during prion disease and open a window for the full understanding of the regulation and role of neurogenesis during chronic progressive neurodegenerative diseases.