Astaxanthin Inhibits Glutamate Release in Rat Cerebral Cortex Nerve Terminals via Suppression of Voltage-Dependent Ca2+ Entry and Mitogen-Activated Protein Kinase Signaling Pathway

The purpose of this study was to examine the effect and mechanism of astaxanthin, a natural carotenoid, on endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes). Results showed that astaxanthin exhibited a dose-dependent inhibition of 4-aminopyridine (4-AP)evoked release of glutamate. The effect of astaxanthin on the evoked glutamate release was prevented by chelating the intrasynaptosomal Ca2+ ions and by the vesicular transporter inhibitor, but was insensitive to the glutamate transporter inhibitor. Astaxanthin decreased depolarization-induced increase in [Ca2+]c, whereas it did not alter the resting synaptosomal membrane potential or 4-AP-mediated depolarization. The effect of astaxanthin on evoked glutamate release was abolished by the N-, P- and Q-type Ca2+ channel blockers, but not by the ryanodine receptor blocker or the mitochondrial Na+/Ca2+ exchanger blocker. In addition, the inhibitory effect of astaxanthin on evoked glutamate release was prevented by the mitogen-activated protein kinase (MAPK) inhibitors PD98059 and U0126. Western blot analyses showed that astaxanthin significantly decreased the 4-AP-induced phosphorylation of MAPK, and this effect was blocked by PD98059. On the basis of these results, it was concluded that astaxanthin inhibits glutamate release from rat cortical synaptosomes through the suppression of presynaptic voltage-dependent Ca2+ entry and MAPK signaling cascade.