Kane C J, Brown G J, Phelan K D
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205,
Neurosci Lett. 1996 Feb 2;204(1-2):93-6. doi: 10.1016/0304-3940(96)12332-6.
The ability of transforming growth factor-beta2 (TGFbeta2) to directly regulate neuronal sensitivity to glutamate and N-methyl-D-aspartate (NMDA) excitotoxicity in rat cerebral cortical neurons was investigated. Mixed neuronal-glial cultures treated with TGFbeta2 (1-10 ng/ml) exhibited a significant 25-50% increase in neuronal death compared to control cultures. TGFbeta2 potentiation of this endogenous glutamate excitotoxicity was blocked by the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate. In addition, neuronal death induced by brief NMDA exposure in both mixed neuronal-glial and pure neuronal cultures was increased by TGFbeta2 (1-30 ng/ml) with a similar dose-response curve. These findings indicate that TGFbeta2, at physiologically relevant concentrations, potentiates NMDA receptor-mediated excitotoxicity and that this occurs independently of TGFbeta2 effects on glia.
研究了转化生长因子-β2（TGFβ2）直接调节大鼠大脑皮质神经元对谷氨酸和N-甲基-D-天冬氨酸（NMDA）兴奋性毒性敏感性的能力。与对照培养物相比，用TGFβ2（1 - 10 ng/ml）处理的混合神经元-胶质细胞培养物中神经元死亡显著增加了25 - 50%。选择性NMDA受体拮抗剂2-氨基-5-磷酸戊酸可阻断TGFβ2对这种内源性谷氨酸兴奋性毒性的增强作用。此外，在混合神经元-胶质细胞培养物和纯神经元培养物中，短暂暴露于NMDA所诱导的神经元死亡在TGFβ2（1 - 30 ng/ml）作用下增加，且具有相似的剂量反应曲线。这些发现表明，在生理相关浓度下，TGFβ2增强了NMDA受体介导的兴奋性毒性，并且这种情况独立于TGFβ2对胶质细胞的作用而发生。
