Enhanced neuronal protection from oxidative stress by coculture with glutamic acid decarboxylase-expressing astrocytes

Astrocytes expressing glutamic acid decarboxylase GAD67 directed by the gli al fibrillary acidic protein promoter were shown to provide enhanced protec tion of PC12 cells from H2O2 treatment and serum deprivation in the presenc e of glutamate. In addition, they protected non-differentiated, but not dif ferentiated, embryonic rat cortical neurons from glutamate toxicity. Glutam ic acid decarboxylase (GAD)expressing astrocytes showed increased glutathio ne synthesis and release compared to control astrocytes. These changes were due to GAD transgene expression, as transient expression of a GAD antisens e plasmid resulted in partial suppression of the increase in glutathione re lease. In addition to the previously demonstrated increases in NADH and ATP levels and lactate release, GAD-expressing astrocytes show increased antio xidant activity, explaining their ability to protect neurons from various i njuries.