Inhibition of glutamate release from rat cerebral cortex nerve terminals by berberine

• Main Authors: Lin, Yu-Wan, 林育琬
• Other Authors: Wang, Su-Jane
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/11277325897393924412

碩士 === 輔仁大學 === 基礎醫學研究所碩士班 === 100 === Berberine, an extracts of Berberis vulgaris, which is a common traditional medicine in India and other countries, has been observed to offer a neuroprotective effect in several in vitro models of neurotoxicity. An excessive release of glutamate is considered to be related to neuropathology of several neurological diseases. The aim of the present study was to investigate the effect and the possible mechanism of berberine on endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes). The results showed that berberine inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). The effect of berberine on the evoked glutamate release was prevented by the chelating extracellular Ca2+ ions, and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Berberine reduced the depolarization-induced increase in the cytosolic free Ca2+ concentration ([Ca2+]c), whereas it did not alter the synaptosomal membrane potential. Further, the effect of berberine on evoked glutamate release was abolished by blocking the Cav2.1 (P/Q-type) channels. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of berberine on evoked glutamate release. Western blot analyses showed that berberine decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). Furthermore, the inhibition of glutamate release by berberine was strongly attenuated in mice without synapsin I. These results show that berberine inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca2+ entry and ERK/synapsin I signaling pathway.