BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons
BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons
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DOI：
10.1016/s0006-8993(97)00195-9
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发表时间：
1997-05-09
期刊：
影响因子：
2.9
通讯作者：
Koizumi, S
中科院分区：
文献类型：
--
作者：
Kume, T;Kouchiyama, H;Koizumi, S
采用原代培养大鼠皮质神经元的方法，观察脑源性神经营养因子(BDNF)对谷氨酸诱导的细胞毒性的影响。脑源性神经营养因子诱导大鼠皮质神经元TrkB酪氨酸磷酸化。N-甲基-D-天冬氨酸非竞争性阻断剂MK-801和一氧化氮合酶阻断剂N-omega-硝基-L-精氨酸可拮抗谷氨酸的细胞毒作用。钙离子载体离子霉素和一氧化氮(NO)供体S亚硝基半胱氨酸(SNOC)和3-吗啉磺胺(SIN-1)也可引起迟发性神经毒性。脑源性神经营养因子孵育10分钟至24小时可保护皮质神经元免受谷氨酸的神经毒性。脑源性神经营养因子对谷氨酸细胞毒性的保护作用与其浓度和孵育时间有关。BDNF还可拮抗离子霉素、SNOC-和SIN-1诱导的细胞毒作用。这些结果表明，BDNF通过减少NO的细胞毒作用，保护培养的皮质神经元免受NMDA受体介导的谷氨酸神经毒性。
The effects of brain-derived neurotrophic factor (BDNF) on glutamate-induced cytotoxicity were examined using primary cultures of rat cortical neurons. BDNF induced TrkB tyrosine phosphorylation in rat cultured cortical neurons. The cell viability was significantly reduced when cultures were briefly exposed to glutamate and incubated with normal medium for 24 h. Glutamate cytotoxicity was prevented by MK-801, which is a non-competitive blocker of N-methyl-D-aspartate and N-omega-nitro-L-arginine, which is a blocker of nitric oxide synthetase. Delayed neurotoxicity was also induced by ionomycin, a calcium ionophore, and nitric oxide (NO) donors such as S-nitrosocysteine (SNOC) and 3-morpholinosydnonimine (SIN-1). Incubating cultures with BDNF for 10 min to 24 h protected cortical neurons against glutamate neurotoxicity. The protective effects of BDNF against glutamate cytotoxicity were dependent on both its concentrations and incubation time. BDNF also prevented the ionomycin-, SNOC-, and SIN-1 induced cytotoxicity. These results indicate that BDNF protects cultured cortical neurons from NMDA receptor-mediated glutamate neurotoxicity by reducing cytotoxic action of NO.