Publication Type Academic Article
Authors Luo J, Kaplitt M, Fitzsimons H, Zuzga D, Liu Y, Oshinsky M, During M
Journal Science
Volume 298
Issue 5592
Pagination 425-9
Date Published 10/11/2002
ISSN 1095-9203
Keywords Genetic Therapy, Glutamate Decarboxylase, Isoenzymes, Neurons, Parkinsonian Disorders, Substantia Nigra, Subthalamic Nucleus
Abstract The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition of the subthalamic nucleus (STN), and excessive activity of the major output nuclei. Using adeno-associated viral vector-mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), the enzyme that catalyzes synthesis of the neurotransmitter GABA, in excitatory glutamatergic neurons of the STN in rats. The transduced neurons, when driven by electrical stimulation, produced mixed inhibitory responses associated with GABA release. This phenotypic shift resulted in strong neuroprotection of nigral dopamine neurons and rescue of the parkinsonian behavioral phenotype. This strategy suggests that there is plasticity between excitatory and inhibitory neurotransmission in the mammalian brain that could be exploited for therapeutic benefit.
DOI 10.1126/science.1074549
PubMed ID 12376704
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