GLUTATHIONE (GSH) is considered the primary molecule responsible for p
eroxide removal from the brain. Inhibition of its rate-limiting synthe
tic enzyme, glutamylcysteine synthetase (GCS), results in morphologica
l damage to both cortical and nigral neurons in rodents. Here, we repo
rt cloning of the catalytic heavy chain GCS mRNA from mouse and its lo
calization in the murine brain. Heavy chain GCS appears to be localize
d in glial populations in the hippocampus, cerebellum and olfactory bu
lb, with lower levels of expression in the cortex and substantia nigra
. Variations in GCS levels and subsequent GSH synthesis may explain di
fferences in susceptibility to neuropathology associated with oxidativ
e stress noted in these various brain regions.