Gene induction of neurotranmitters and neurotrophic factors for the treatment of Parkinson's disease

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Parkinson's disease is a neurodegenerative disorder of nigrostriatal dopaminergic system. Methods to deliver dopamine or neurotrophic factors such as GDNF are expected to be applied for neuroprotection and repair of this system. In order to deliver these factors, gene induction into the striatum is a useful method. We developed a method to inject plasmid vector and liposome complex of these genes continuously into the striatum. For Parkinson's disease model, 6-OHDA injection was performed into the unilateral striatum and analyses were performed as follows : 1)TH immunostaining for histology and number of dopamine neurons in the substantia nigra and density of dopaminergic fibers in the striatum are measured, 2)HPLC analyses of dopamine content in the host striatum, 3)rotational behavior after injection of amphetamine or apomorphine into the host.We could clarify the points below during the research period.1.Gene induction of GDNF and TH could be performed efficiently in the glia of host striatum2.The period of gene induction after 6-OHDA lesion was critical to get functional improvement3.Simultaneous induction of GDNF and TH genes was more efficient.4.Regarding neurotrophic factor genes, simultaneous gene induction of both GDNF and BDNF genes were more effective.5.Because gene expression was weakened at 6 months after induction, long-term expression of gene was important for future study.These results indicate the efficacy of neurotransmitter and neurotrophic factor gene induction into the striatum for the treatment of Parkinson's disease.