Neuroreport
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Transient global ischemia induces selective hippocampal pyramidal neuronal death. Under conditions of severe ischemic hypoxia, hypoxia-inducible factor-1α (HIF-1α) induces apoptosis. Exendin-4 (Ex-4), the glucagon-like peptide-1 receptor (GLP-1R) agonist, provides neuroprotection against brain damage after cerebral ischemia. ⋯ These in-vivo results were confirmed in vitro in SH-SY5Y cells and primary cortical neurons treated with 100 nM of Ex-4 under hypoxic conditions (0.1%>O2). We found that Ex-4 decreased the HIF-1α expression in the SH-SY5Y cell line and primary cortical neurons under hypoxic conditions, and this effect was reversed by cotreatment with exendin (9-39), a GLP-1R antagonist. These results suggest that HIF-1α may be involved in the neuroprotective effect of Ex-4 in the hypoxia-damaged brain.