Subthalamic GAD gene therapy in a Parkinson's disease rat model Academic Article uri icon

Overview

MeSH Major

  • 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.

publication date

  • October 11, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1074549

PubMed ID

  • 12376704

Additional Document Info

start page

  • 425

end page

  • 9

volume

  • 298

number

  • 5592