| Parkinson's disease (PD) is characterized by a common degeneration of central nervous system(CNS). The pathologic feature is selective degeneration of dopaminergic (DA) neurons in the substantia nigra of the midbrain. Grafts of embryonic ventral mesencephalon (VM) can survive and reduce motor symptoms after transplantation into the brains of Parkinson's patients and animal models of Parkinson's disease . Although transplantation is a promising treatment for Parkinson's disease, its clinical application has been limited to a few cases, because it is very difficult to obtain large numbers of human embryonic mesencephalic tissues. To overcome this problem, various candidate cells have been taken as possible donor cells for transplantation therapy for Parkinson's disease.Mesencephalic neural stem cells derived from the developing midbrain appear to be a good candidate cell source for dopaminergic neurons.Neural stem cells (NSCs) are characterized by 1) undifferentiated feature,2)self-renewing capacity,3)multipotentiality. In the other words, NSCs can be taken,cultured for a long time and proliferate in vitro. NSCs can differentiate into neurons, astrocyte and oligodendrocyte , induced by some factors. However, unlike neural stem cells derived from the telencephalic SVZ, these cells have transcription factors characteristic of their midbrain origin and can respond to regional signals by rapidly differentiating as DA neurons . Because of these features, these cells provide an especially appropriate cellular source for generating DA neurons in vitro. The extract from DA-depleted striatum exhibited trophic effect, concentration- dependently, on cell survival and neurite extension of DA neurons. However, there are no data about the effects of striatal extracts on production of DA neurons from mesencephalic NSCs. In the present study, mesencephalic NSCs obtained from developing rat mesencephalic flexure were differentiated into DA neurons in the presence of striatal extracts and the induced DA neurons have functional effects after intrastriatal transplantation in the rat Parkinson model. The main methods and results are as follows:1. Mesencephalic NSCs were isolated, indentified and proliferated in vitro.2.Mesencephalic NSCs could differentiated into neurons, astrocytes and oligodendrocytes in vitro.3. In the presence of striatal extracts , about 20% of mesencephalic NSCs were induced into dopaminegic neurons.4. NSCs and striatal extracts-induced NSCs were transplanted in the head of the caudate-putamen ipsilateral to the 6-OHDA lesion of rats. At different time after transplantation, the rats were test for apomorphine-induced rotation.The rotation of rats that have received gratfs of striatal extracts-induced NSCs revealed decreasing apparently 6 weeks after tranplantation comparerd with the control graft group and NSCs group. In conclusion ,we isolated, indentified and proliferated mesencephalic NSCs in vitro and the NSCs could be induced into dopaminergic neurons in the presence of striatal extracts. The induced mesencephalic NSCs grafts provided partial amelioration of apomorphine- induced rotational asymmetry after transplanted. The result suggest that striatal extracts may contribute to more efficient production of DA neurons from mesencephalic NSCs ,and that this may be related to an enhancement of generation and/or survival of DA cells.It showed a splendid future of applying on the treatment of Parkinson's disease.However, further investigation is needed for better understanding the mechanism of the induced effect and how to rise the the induced percentage of DA neurons.
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