HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

Abstract
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.
AuthorsB Lee, H Lee, Y R Nam, J H Oh, Y H Cho, J W Chang
JournalGene therapy (Gene Ther) Vol. 12 Issue 15 Pg. 1215-22 (Aug 2005) ISSN: 0969-7128 [Print] England
PMID15829994 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glutamate Decarboxylase
Topics
  • Adenoviridae (genetics)
  • Animals
  • Behavior, Animal
  • Cells, Cultured
  • Cytomegalovirus (genetics)
  • Electrocardiography
  • Gene Expression
  • Genetic Therapy (methods)
  • Glutamate Decarboxylase (genetics, metabolism)
  • Humans
  • Male
  • Models, Animal
  • Parkinson Disease (physiopathology, therapy)
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Subthalamic Nucleus (metabolism)
  • Transduction, Genetic (methods)
  • Transfection (methods)
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: