17β-Estradiol reduces cortical lesion size in the glutamate excitotoxicity model by enhancing extracellular lactate:: a new neuroprotective pathway
17β-Estradiol reduces cortical lesion size in the glutamate excitotoxicity model by enhancing extracellular lactate:: a new neuroprotective pathway
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DOI：
10.1016/s0006-8993(01)02359-9
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发表时间：
2001-05-18
期刊：
影响因子：
2.9
通讯作者：
Gratzl, O
中科院分区：
文献类型：
--
作者：
Mendelowitsch, A;Ritz, MF;Gratzl, O
雌激素在神经元功能和保护大脑皮层神经元免受病理条件的影响方面起着重要作用。在谷氨酸兴奋毒性的体内模型中，通过微透析探针将谷氨酸施加到大鼠皮层，已经被用于研究17 β-雌二醇启动的神经保护过程。大鼠用17 β-雌二醇（i. v.）然后通过微透析探针将100 mM谷氨酸盐局部应用于皮层。用17 β-雌二醇预处理显著减小了谷氨酸诱导的皮质病变的大小。在从探针收集的皮质微透析液中，在施用谷氨酸后立即观察到乳酸峰。在17 β-雌二醇预处理后，在谷氨酸盐应用后120分钟，使用雌二醇的乳酸盐峰值显著高于不使用雌二醇的乳酸盐峰值，在测量结束时达到700%的基础水平。细胞外葡萄糖水平在17 β-雌二醇预处理和未预处理的情况下均显著降低。用α-氰基-4-羟基肉桂酸（4-CIN）局部阻断神经元乳酸转运蛋白完全消除了17 β-雌二醇的神经保护作用，并诱导了更大的皮质病变。在抑制乳酸转运蛋白后观察到细胞外乳酸的积累，表明乳酸转运到神经元中是17 β-雌二醇的神经保护作用所必需的。抗雌激素他莫昔芬也消除了17 β-雌二醇对损伤大小的神经保护作用，并抑制乳酸的产生。这些结果表明，17 β-雌二醇通过激活谷氨酸刺激的乳酸产生的新的神经保护机制，这是雌激素受体依赖性的。(C)2001爱思唯尔科技有限公司。保留所有权利。
Estrogens play an important role in neuronal function and in protecting neurones in the cerebral cortex against pathological conditions, An in vivo model of glutamate excitotoxicity in which glutamate is applied to the cortex of rats through a microdialysis probe has been used to investigate the neuroprotective processes initiated by 17 beta -estradiol. Rats were pre-treated with 17 beta -estradiol (i.v.) before local application of 100 mM glutamate into the cortex through a microdialysis probe. Pre-treatment with 17 beta -estradiol significantly reduced the size of the glutamate-induced cortical lesion. In the cortical microdialysates collected from the probe, a peak of lactate was observed immediately after glutamare application. After 17 beta -estradiol pre-treatment this peak of lactate was significantly higher with estradiol than without 120 min after glutamate application, reaching 700% basal level at the end of measurement. The level of extracellular glucose was markedly decreased with and without 17 beta -estradiol pre-treatment. Local blockage of neuronal lactate transporters with alpha -cyano-4-hydroxycinnamate (4-CIN) completely abolished the neuroprotective effect of 17 beta -estradiol and induced a larger cortical lesion. An accumulation of extracellular lactate was observed after inhibition of the lactate transporters suggesting that transport of lactate into neurones is necessary for the neuroprotective effect of 17 beta -estradiol. The anti-estrogen tamoxifen also abolished the neuroprotective effect of 17 beta -estradiol on the lesion size and inhibited the production of lactate. These results suggest a new neuroprotective mechanism of 17 beta -estradiol by activating glutamate-stimulated lactate production, which is estrogen receptor-dependent. (C) 2001 Elsevier Science B.V. All rights reserved.