title: The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain.
abstract: There are many indications that neurogenesis is impaired in Parkinson's disease, which might be due to a lack of dopamine in the subventricular zone. An impairment in neurogenesis may have negative consequences for the development of new therapeutic approaches in Parkinson's disease, as neural stem cells are a potential source for endogenous repair. In this study, we examined the subventricular zone of 10 patients with Parkinson's disease and 10 age- and sex-matched controls for proliferation and neural stem cell numbers. We also included five cases with incidental Lewy body disease, which showed Parkinson's disease pathology but no clinical symptoms and thus did not receive dopaminergic treatment. We quantified the neural stem cell number and proliferative capacity in the subventricular zone of these three donor groups. We found subventricular neural stem cells in each donor, with a high variation in number. We did not observe significant differences in neural stem cell number or in proliferation between the groups. Additionally, we were able to culture neural stem cells from post-mortem brain of several patients with Parkinson's disease, confirming the presence of viable neural stem cells in these brains. We have also examined the subventricular zone of a chronic, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model, and again found no effect of dopaminergic denervation on precursor proliferation. Lastly, we investigated the proliferation capacity of two different human neural stem cell lines in response to dopamine. Both cell lines did not respond with a change in proliferation to treatment with dopamine agonists and an antagonist. In summary, the adult neural stem cell pool in the subventricular zone was not clearly affected in the human parkinsonian brain or a Parkinson's disease mouse model. Furthermore, we did not find evidence that dopamine has a direct effect on human neural stem cell proliferation in vitro. Thus, we conclude that the number of adult neural stem cells is probably not diminished in the parkinsonian brain and that dopamine depletion most likely has no effect on human neural stem cells.
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Simone A
authors.initials: SA
authors.lastname: van den Berge
authors.forename: Miriam E
authors.initials: ME
authors.lastname: van Strien
authors.forename: Joanna A
authors.initials: JA
authors.lastname: Korecka
authors.forename: Anke A
authors.initials: AA
authors.lastname: Dijkstra
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Sluijs
authors.forename: Lieneke
authors.initials: L
authors.lastname: Kooijman
authors.forename: Ruben
authors.initials: R
authors.lastname: Eggers
authors.forename: Lidia
authors.initials: L
authors.lastname: De Filippis
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Vescovi
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.forename: Wilma D J
authors.initials: WD
authors.lastname: van de Berg
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D058953:Neural Stem Cells; D055495:Neurogenesis / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology