Artikel
Transplantation (TX) of rostral migratory stream (RMS)-derived cells into a rat model of Parkinson’s disease (PD)
Transplantation von Zellen des rostralen migratorischen Stroms in ein Parkinson’sches Rattenmodell
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Parkinson’s disease (PD) is a severe neurodegenerative disorder due to the loss of dopaminergic neurons mainly in the nigrostriatal system. Since promising strategies for treating PD as the neurotransplantation of foetal brain tissue pose considerable ethical constraints, we sought for alternative cell sources. The finding that the adult mammalian brain possesses stem/progenitor cells with the potential of migration and differentiation, may point to a new source of cells exploitable for neurotransplantation. Throughout adult life persisting neural stem cells of the subventricular zone (SVZ) and RMS generate neuroblasts which migrate over a long distance and ultimately differentiate into tyrosinhydroxylase positive (TH+) and GABAergic interneurons in the olfactory bulb. The purpose of this study was to determine whether neuroblasts of the forebrain might help to restore the dopaminergic system.
Methods
Juvenile RMS as well as embryonic ventral mesencephalon (VM) of β-actine EGFP mice were explanted, dissociated, and subsequently transplanted into the striatum of 6-hydroxydopamine unilaterally lesioned immunosuppressed rats. The lesion and the graft effect were evaluated by apomorphine and amphetamine drug induced rotation tests. For quantitative and qualitative morphological analysis immunocytochemistry against TH and doublecortin (DCX), a marker for migrating cells, was performed.
Results
Drug induced rotation test pointed out a significant recovery within the VM grafted animals (n=10, rotation mean: apo -9,6 pre to -3,0 post and amph.15,1 pre to -2,8 post TX) but only a tendency in the apomorphine rotation within the RMS group (n=20 apo -8,5 pre to -6,3 post TX). Immunohistological analysis revealed in the RMS-grafts GFP positive cells which were widely distributed in the host striatum showing elaborate dendritic arborizations covered by spines. Further confocal morphological analysis of the grafted cells unveil the coexistence of non-differentiated (DCX positive) cells and well differentiated neurons. In the VM grafted group we could see strong graft survival and substantial TH-positive reinnervation.
Conclusions
Taken together, the rat model of PD is a highly useful tool to investigate the morphological and functional integration of grafted neural stem cells.