PMID: 9436790Jan 22, 1998Paper

Glutamate-modulated production of GABA in immortalized astrocytes transduced by a glutamic acid decarboxylase-expressing retrovirus

Glia
S SacchettoniB Jacquemont

Abstract

Replication-defective Moloney murine leukemia virus expressing the GAD67 gene under the control of the GFAP promoter was produced using selected clones of a fibroblast-packaging cell line. A spontaneously immortalized astrocyte cell line was infected with this virus and cellular clones expressing GAD67 selected. Astrocyte and fibroblast clones expressed functional GAD (detected by glutamic acid decarboxylation), but only fibroblasts were able to also produce GABA in the extracellular medium. When exposed to 200 microM glutamate, despite an observed difference in the rates of glutamate accumulation in control and GAD67-expressing astrocytes, similar proportions of glutamate taken up were detected. In GAD67-expressing astrocytes, the glutamate was mainly converted into GABA, suggesting GAD transgene activity to be dominant over other glutamate metabolic pathways, such as glutamine synthetase and glutamate dehydrogenase. Moreover, rapid GABA release into the cell medium was also observed, suggesting the involvement of reverse GABA transporters. The use of the GFAP promoter might be able to take advantage of its activation in response to factors inducing reactive gliosis observed in pathological insults. GAD67-expressing astrocytes...Continue Reading

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Citations

Oct 22, 2003·Neurosurgery Clinics of North America·Mary E Garrity-MosesNicholas M Boulis
Apr 12, 2001·The European Journal of Neuroscience·R Gutiérrez, U Heinemann
Aug 23, 2008·Epilepsia·Véronique RibanMatthew J During
Apr 24, 2007·American Journal of Physical Medicine & Rehabilitation·Shearwood McClellandNicholas M Boulis

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