博士 / 輔仁大學 / 化學系 / 106 / The flavonoids, hesperidin and apigenin, could cross the blood-brain barrier. Given the involvement of glutamate neurotoxicity in the pathogenesis of neurodegenerative disorders, this study was conducted to evaluate the potential role in glutamate release and glutamate neurotoxicity in rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), these two agents inhibited glutamate release and the elevation of the cytosolic free Ca2+ concentration evoked by 4-aminopyridine (4-AP). The hesperidin and apigenin -mediated inhibition of 4-AP-evoked glutamate release was prevented by chelating the extracellular Ca2+ ions and blocking Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel activity. Furthermore, in slice preparations, whole-cell patch-clamp experiments showed that they reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, suggesting a presynaptic mechanism. On the basis of these results, we suggested that hesperidin and apigenin exert their presynaptic inhibition probably by reducing Ca2+ entry mediated by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, thereby inhibiting glutamate release from the rat hippocampal nerve terminals. In addition, intraperitoneal (i.p.) injection of kainic acid (KA, 15 mg/kg) elevated the extracellular glutamate levels and caused the considerable neuronal loss in the hippocampal CA3 area. These KA-induced alterations were attenuated by pretreatment with hesperidin (10 or 50 mg/kg, i.p.) before administering the KA. These results demonstrate that hesperidin inhibits 4-AP evoked glutamate release in vitro and attenuates in vivo KA-induced neuronal death in the hippocampus. Our findings indicate that hesperidin and apigenin could decrease glutamate release by pre-synaptic mechanism and may be promising candidates for neuroprotection.
| Identifer | oai:union.ndltd.org:TW/106FJU00065006 |
| Date | January 2018 |
| Creators | CHANG, CHIA-YING, 張家穎 |
| Contributors | WANG, SU-JANE, CHOU, SHANG-SHING P, 王素珍, 周善行 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 104 |
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