Glutamic acid decarboxylase-expressing astrocytes exhibit enhanced energetic metabolism and increase PC12 cell survival under glucose deprivation

Astrocytes play a key role by catabolizing glutamate from extracellular spa ce into glutamine and tricarboxylic acid components. We previously produced an astrocytic cell line that constitutively expressed glutamic acid decarb oxylase (GAD67), which converts glutamate into GABA to increase the capacit y of astrocytes to metabolize glutamate. In this study, GAD-expressing astr ocytes in the presence of glutamate were shown to have increased energy met abolism, as determined by a moderate increase of 3-(4,5-dimethylthiazol-2-y l)-2,5-diphenyltetrazolium bromide reduction, by an increased ATP level, an d by enhanced lactate release. These changes were due to GAD transgene expr ession because transient expression of a GAD antisense plasmid resulted in partial suppression of the ATP level increase. These astrocytes had an incr eased survival in response to glucose deprivation in the presence of glutam ate compared with the parental astrocytes, and they were also able to enhan ce survival of a neuronal-like cell line (PC12) under glucose deprivation. This protection may be partially due to the increased lactate release by GA D-expressing astrocytes because PC12 cell survival was enhanced by lactate and pyruvate under glucose deprivation. These results suggest that the esta blishment of GAD expression in astrocytes enhancing glutamate catabolism co uld be an interesting strategy to increase neuronal survival under hypoglyc emia conditions.