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- W296893669 abstract "The loss of dopaminergic neurons of the nigrostriatal pathway is central to the pathogenesis of Parkinson's disease (PD). The neurotrophic factors growth/differentiation factor-5 (GDF-5) and glial cell line derived neurotrophic factor (GDNF) have been shown to protect the nigrostriatal dopaminergic pathway in rats which develop Parkinsonian symptoms following administration of the selective dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA). The aim of this project is to deliver cDNAs for these factors into the striatum of parkinsonian rats using viral vectors. The model of PD which we will use involves stereotaxic injection of 6-OHDA into the adult rat striatum, which induces progressive degeneration of the nigrostriatal pathway. We will compare the ability of each viral vector to deliver the neurotrophins and to improve motor function in these rats. The vectors used in the present study are Adeno-associated virus type 2 (AAV-2) vector and a lentiviral vector derived from HIV, pseudotyped with Vesicular Stomatitis virus G protein. Each vector has distinct advantages. We have constructed an AAV-2 vector expressing GDF-5, under the control of the CMV promoter. To trace gene expression, we have used the reporter gene enhanced green fluorescent protein (EGFP), linked by an internal ribosome entry sequence. The plasmid has been shown to express GDF-5 by western analysis and EGFP by fluorescence microscopy in transfected BHK and CHO cells and vector particles constructed using this plasmid have been used to transduce HEK293 cells and HT1080 cells. We have injected lentiviral vector particles expressing GDF-5 or GDNF unilaterally into the striatum of adult male Wistar rats anaesthesized using intraperitoneal injection of sodium pentobarbitone. Two weeks later, the rats received a 6-OHDA injection into the ipsilateral striatum. The neuroprotective effects of the vector are being measured using the following behavioural tests: amphetamine-induced rotation, stepping test, cylinder test and placement test." @default.
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- W296893669 date "2004-12-01" @default.
- W296893669 modified "2023-09-28" @default.
- W296893669 title "P7: Viral vectors to deliver neurotrophin genes to a rat model of Parkinson's disease" @default.
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