Glia in health and disease

Neural stem cells in the adult brain

Neural progenitors in the astrocytic ribbon in the human brain

The subventricular zone (SVZ) is a principal source of neural progenitors in the adult mammalian brain. In the rodent brain this region continuously generates new neurons for the olfactory bulb. The astrocytes in the SVZ have been identified as multipotent neural progenitors, which are the precursors of newly generated neurons in the adult brain. Recently it has also been shown that human astrocytes from the SVZ area, that form a ribbon lining the ventricles, divide in vivo and produce multipotent self-renewing neurospheres in vitro. Our group has found a specific marker for the human astrocytic ribbon. We have shown that astrocytes in the human brain germinal zones express a specific isoform of the glial fibrillary acidic protein (GFAP), i.e. GFAP-δ.

The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain 
Human brainThere 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. Van den Berge et al. Brain 2011 134:3249-3263.

delta tulpen

Discussion: quantification neural stem cells in human SVZ  

October 2012 - Our work on endogenous neural stem cells has been identified as a highlight of the ECNP meeting in Vienna (click picture for video : 11:40-14:45 min).brain