Stem cell deficiency in Parkinson's disease

Neural precursor cells are newly born throughout adulthood in the subventricular (SVZ) zone of the basal ganglia and in the sugbranular zone of the hippocampus in mammals. These precursor cells integrate into the brain as functional interneurons. We demonstrated that a dopaminergic innervation exists in both of these regions. In the SVZ, dopaminergic fibers were found in immediate vicinity of highly proliferate precursor cells. The precursor cells expressed dopamine receptors. An experimental ablation of the dopaminergic afferents reduced the proliferation rate of these precursors, and the generation and integration of new-born neurons. Restoration of the dopaminergic neurotransmission using levodopa or a dopamine agonist also restored the production of neural precursor cells. In the brains of patients having died with Parkinson's disease, characterised by a loss of brain dopamine levels of at least 80%, we also found a significant reduction of endogenous adult neurogenesis. These data support the view, that in the brains of patients with Parkinson's disease, neurogenesis might be impaired as a consequence of dopamine depletion. We propose the hypothesis, that chronic reduction of adult neurogenesis in Parkinson's disease might lead to structural changes in the brain that could underlie non-motor symptoms frequently observed in these patients.