Carnosine Protects GT1-7 Cells Against Zinc-induced Neurotoxicity: a Possible Candidate for Treatment for Vascular Type of Dementia

Abstract

Zinc is the second most abundant trace element in the brain. Considerable amount of zinc is co-released with glutamate to the synaptic cleft during the neuronal excitation. Recent studies have indicated that excess zinc has a causative role in delayed neuronal death after transient global ischemia ischemia. Therefore, it is possible that a substance which protects against zinc-induced neuronal death could be a candidate for the prevention or treatment of neurodegeneration after ischemia, and finally provide a clue to the drugs of vascular type of senile dementia. To explore such substances, we have developed a convenient and sensitive in vitro assay system using GT1-7 cells (immortalized hypothalamic neurons), and examined various substances including fish extracts. Among tested, we found that water-soluble, heat-stable extracts of eels significantly protected GT1-7 cells from zinc. The eel extract contained much amount of carnosine (β-alanyl histidine), and carnosine protected GT1-7 cells against zinc-induced neurotoxicity in a dose-dependent manner. Our results suggest that carnosine may become a candidate for a therapeutic target of the global ischemia.