Objective: To analyze if the adult rostral migratory stream (RMS) harbors neural stem cells with the potential to create dopaminergic neurons for the olfactory bulb (OB) and therefore represents a possible source for stem cell therapies in Parkinson’s disease.

Background: Neurogenesis occurs from stem cells in the subventricular zone (SVZ) in the adult mammalian brain. They supply neuroblasts via the rostral migratory stream (RMS) to the OB, where they differentiate partly into dopaminergic neurons. While the RMS has been considered as a connecting pathway only, its potential to act as neurogenic niche itself under certain circumstances has just recently been suggested.

Methods: To investigate stem cells residing in the RMS of adult mice, we interrupted the influx of neuroblasts from the SVZ into the RMS mechanically by implanting a physical barrier. We then stopped the generation of neuroblasts by infusing the antimitotic drug cytarabine (Ara-C) for 6 days. Thereafter, we injected bromodeoxyuridine(BrdU) and sacrificed the mice in a time course, to study if stem cell proliferation within the RMS would occur to generate neuroblasts migrating to and differentiating in the OB. Therefore, we co-immunostained the RMS, OB and SVZ with antibodies against BrdU and cell type markers (nestin, Pax6, GFAP, NeuN).

Results: After experimental depletion of neuroblast influx from the SVZ, the RMS itself acted as neurogenic niche, with proliferation of nestin+ and Pax6+ cells downstream of the barrier. Despite the interruption of the RMS, the number of newborn periglomerular cells downstream of the barrier remained stable, whereas the number of newborn granular cells was highly reduced. Among the newborn periglomerular cells, we observed a high rate of differentiation into a dopaminergic phenotype downstream of the barrier. Thus, the total number of dopaminergic cells in the OB did not change.

Conclusions: Our work suggests that the RMS functions as a neurogenic niche, which is activated upon interruption of neuroblast migration from the SVZ. The fact, that the physical barrier reduced the number of newborn granular neurons, but not of newborn dopaminergic periglomerular neurons in the OB, suggests that the first is predominantly generated within the SVZ, and the latter predominantly within the RMS. Thus, the RMS may constitute a potential source to collect stem cells for cell replacement therapies in Parkinson’s disease.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/dopaminergic-stem-cells-reside-in-the-rostral-migratory-stream/