Dopaminergic trophism after intrastriatal injection of lentivirus-transferred GDNF in Parkinson rat model.
To investigate the effects of lentivirus-mediated transfection of GDNF on Parkinson  s disease (PD). The pNL-gdnf plasmid was constructed by replacing the LacZ-coding region present in pNL-lacZ/CMV. Vector particles involved a three-plasmid lentivirus expression system were co-transferred into 293T cells through calcium phosphate method. High-titer virus was collected from infected 293T cells and injected into lesion-side striatum of PD rats, and their apomorphine-induced rotations were assayed at day 14, 30 and 60, respectively. GDNF protein was detected by Western blot analysis, and the expression of lacZ and TH were detected by immunochemistry. Results showed that behavioral recovery gradually appeared after transplantation, and a significant reduction in the rotational response was observed at the 14th day. Meanwhile, gdnf expression maintained for at least 60 d, which had dopaminergic trophism to a certain degree, indicating that lentivirus-mediated transfection gdnf could effectively improve the clinical function of PD rats, which provide a potential attractive tool of gene therapy for PD.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D002540:Cerebral Cortex / Q000737:chemistry; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D018491:Dopamine Agonists; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine