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Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models

 B Lee  ;  H Lee  ;  Y R Nam  ;  J H Oh  ;  Y H Cho  ;  J W Chang 
 GENE THERAPY, Vol.12(15) : 1215-1222, 2005 
Journal Title
Issue Date
Adenoviridae/genetics ; Animals ; Behavior, Animal ; Cells, Cultured ; Cytomegalovirus/genetics* ; Electrocardiography ; Gene Expression ; Genetic Therapy/methods* ; Glutamate Decarboxylase/genetics* ; Glutamate Decarboxylase/metabolism ; Humans ; Male ; Models, Animal ; Parkinson Disease/physiopathology ; Parkinson Disease/therapy* ; Promoter Regions, Genetic* ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus/metabolism* ; Transduction, Genetic/methods ; Transfection/methods ; Treatment Outcome
In this study, we report the amelioration of parkinsonian symptoms in rat Parkinson's disease (PD) models, as a result of the expression of glutamate decarboxylase (GAD) 65 with a modified cytomegalovirus (CMV) promoter. The transfer of the gene for gamma-amino butryic acid (GAD), the rate-limiting enzyme in gama-amino butrylic acid (GABA) production, has been investigated as a means to increase inhibitory synaptic activity. Electrophysiological evidence suggests that the transfer of the GAD65 gene to the subthalamic nucleus (STN) can change the excitatory output of this nucleus to inhibitory output. Our in vitro results also demonstrated higher GAD65 expression in cells transfected with the JDK promoter, as compared to cells transfected with the CMV promoter. Also, a rat PD model in which recombinant adeno-associated virus-2 (rAAV2)-JDK-GAD65 was delivered into the STN exhibited significant behavioral improvements, as compared to the saline-injected group. Interestingly, we observed that these behavioral improvements were more obvious in rat PD models in which rAAV2-JDK-GAD65 was injected into the STN than in rat PD models in which rAAV2-CMV-GAD65 was injected into the STN. Moreover, according to electrophysiological data, the rAAV2-JDK-GAD65-injected group exhibited more constant improvements in firing rates than did the rAAV2-CMV-GAD65-injected group. These data indicate that the JDK promoter, when coupled with GAD65 expression, is more effective with regard to parkinsonian symptoms than is the CMV promoter.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Oh, Jin Hwan(오진환)
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
Cho, Yoon Hee(조윤희)
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