Astaxanthin inhibits glutamate release in rat cerebral cortex nerve terminals via modulation of MAPK signaling pathway
演題番号 : P1-b01
Su Jane Wang:1 Tzu Yu Lin:1 Cheng Wei Lu:1
1:Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan 2:Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao, Taipei County, Taiwan
The purpose of this study was to examine the effect of astaxanthin 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 the chelating 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 blocker, but not by the ryanodine receptor blocker, or the mitochondrial Na+/Ca2+ exchanger blocker. The inhibitory effect of astaxanthin on evoked glutamate release was inhibited by the mitogen-activated protein kinase (MAPK) inhibitors, and astaxanthin significantly decreased the depolarization-induced phosphorylation of MAPK. On the basis of these results, it was concluded that the inhibitory effect of astaxanthin on evoked glutamate release is linked to a decrease in [Ca2+]i contributed by Ca2+ entry through presynaptic voltage-dependent Ca2+ channels and to the subsequent suppression of the MAPK signaling cascade.