Monnerie Hubert, Le Roux Peter D
Department of Neurosurgery, University of Pennsylvania, 330 S 9th Street, 4th Floor, Philadelphia, PA 19107, USA.
Exp Neurol. 2007 Jun;205(2):367-82. doi: 10.1016/j.expneurol.2007.02.007. Epub 2007 Feb 22.
The vulnerability of brain cells to neurologic insults varies greatly, depending on their neuronal subpopulation. However, cells surviving pathological insults such as ischemia or brain trauma may undergo structural changes, e.g., altered process growth, that could compromise brain function. In this study, we examined the effect of glutamate excitotoxicity on dendrite growth from surviving cortical GABAergic neurons in vitro. Glutamate exposure did not affect GABAergic neuron viability, however, it significantly reduced dendrite growth from GABAergic neurons. This effect was blocked by the AMPA receptor antagonists NBQX and CFM-2, and mimicked by AMPA, but not NMDA. Glutamate excitotoxicity also caused an NMDA receptor-mediated decrease in the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67) immunoreactivity from GABAergic neurons, measured using immunocytochemical and Western blot techniques. GAD is necessary for GABA synthesis; however, reduction of GABA by 3-mercaptopropionic acid (3-MPA), which inhibits GABA synthesis, did not alter dendrite growth. These results suggest that GABAergic cortical neurons are relatively resistant to excitotoxic-induced cell death, but they can display morphological and biochemical alterations which may impair their function.
脑细胞对神经损伤的易感性差异很大，这取决于它们的神经元亚群。然而，在诸如缺血或脑外伤等病理损伤中存活下来的细胞可能会发生结构变化，例如突起生长改变，这可能会损害脑功能。在本研究中，我们在体外研究了谷氨酸兴奋性毒性对存活的皮质GABA能神经元树突生长的影响。谷氨酸暴露不影响GABA能神经元的活力，然而，它显著减少了GABA能神经元的树突生长。这种效应被AMPA受体拮抗剂NBQX和CFM-2阻断，并被AMPA模拟，但不被NMDA模拟。谷氨酸兴奋性毒性还导致NMDA受体介导的GABA能神经元中GABA合成酶谷氨酸脱羧酶（GAD65/67）免疫反应性降低，这是使用免疫细胞化学和蛋白质印迹技术测量的。GAD是GABA合成所必需的；然而，用抑制GABA合成的3-巯基丙酸（3-MPA）降低GABA水平并没有改变树突生长。这些结果表明，GABA能皮质神经元对兴奋性毒性诱导的细胞死亡相对具有抗性，但它们可能会表现出形态和生化改变，这可能会损害其功能。
