Hippocampal glutamine synthetase: insensitivity to glucocorticoids and stress

Glucocorticoids enhance the neurotoxic potential of several insults to the rat hippocampus that involve overactivation of glutamatergic synapses. These hormones also stimulate the synthesis of glutamine synthetase (GS) in peripheral tissue. Because this enzyme helps regulate glutamate metabolism in the central nervous system, glucocorticoid induction of GS in the brain may underlie the observed synergy. We have measured GS activity in the hippocampus and skeletal muscle (plantaris) of adult rats after bilateral adrenalectomy (ADX), corticosterone (Cort) replacement, or stress. No significant changes in GS were observed in hippocampal tissue, whereas muscle GS was significantly elevated after Cort treatment or stress and was reduced after ADX. These results suggest that Cort-induced shifts in GS activity probably do not explain Cort neurotoxicity, although the stress-induced rise in muscle GS may be relevant to certain types of myopathy.