Astrocyte synthetic pathways, dependent on glutathione, are involved in cerebrovascular reactivity to CO<sub>2</sub> Reductions in glutathione levels in aging, stroke, or schizophrenia could lead to dysfunctional regulation of CBF and subsequent neuronal damage.<b>SIGNIFICANCE STATEMENT</b> Neuronal activity leads to the generation of CO<sub>2</sub>, which has previously been shown to evoke cerebral blood flow (CBF) increases via the release of the vasodilator PgE<sub>2</sub> We demonstrate that hypercapnia (increased CO<sub>2</sub>) evokes increases in astrocyte calcium signaling, which in turn stimulates COX-1 activity and generates downstream PgE<sub>2</sub> production.
We found that levels of prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin-endoperoxide receptor 3 (PTGER3) mRNA are increased, and levels of prostaglandin-endoperoxide synthase 2 (PTGS2; aka COX-2) mRNA are decreased, in older subjects with schizophrenia (> 40years of age) compared to matched normal controls or younger subjects with schizophrenia (< 40years of age).