Gene-based neurotransmitter modulation in cerebellar granule neurons.

Fritz JD, Utz AL, Hale NM, Wu L, Powers AC, Verdoorn TA, Robertson D
J Neurochem. 1997 68 (1): 204-12

PMID: 8978727 · DOI:10.1046/j.1471-4159.1997.68010204.x

The human glutamic acid decarboxylase (GAD) gene was transferred into rat cerebellar granule neurons. Following adenoviral-mediated gene transfer, nearly 100% of the neurons had transgene expression that persisted for the duration of their survival in culture. GABA levels were elevated both in the growth media and in lysates of GAD-modified granule neurons. In GAD-modified neurons, extracellular GABA levels steadily increased with time, whereas intracellular GABA levels peaked 10 days after gene transfer. GAD-modified neurons released both glutamate and GABA into the surrounding media before and after potassium-induced stimulation, but only the release of glutamate was sensitive to potassium stimulation. These data suggest that glutamatergic neurons, which initially contained no detectable GABA, can be genetically modified to release GABA constitutively.

MeSH Terms (13)

Adenoviridae Animals Cells, Cultured Cerebellum gamma-Aminobutyric Acid Gene Transfer Techniques Glutamate Decarboxylase Glutamic Acid Humans Neurons Neurotransmitter Agents Rats Rats, Sprague-Dawley

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