ADRENAL STEROID REGULATION OF NOS ISOFORMS

肾上腺类固醇皮质酮是已知的， 海马体的神经毒性 皮质类固醇被建议用于 导致神经毒性事件，如缺氧、缺血和 通过增强突触中谷氨酸的活性来降低低血糖， 其最终导致一氧化氮合酶（NOS）的活化。 然而，除了增强谷氨酸盐的作用外， 皮质类固醇也可以通过调节这些事件， NOS亚型的表达。 因此，本提案的目的是 研究皮质类固醇对实验性大鼠脑内NOS亚型的调节作用， 范式产生应激诱导的神经元萎缩， 海马体。海马一氧化氮合酶亚型表达的变化 采用原位杂交组织化学方法进行检测。 的能力 抑制皮质类固醇介导的神经元损伤的NOS活性抑制剂 还将评估萎缩。 这些研究将有助于更好地 了解潜在的分子机制， 皮质类固醇在应激期间产生神经元萎缩。 此外，本发明还提供了一种方法， 这些结果可能有助于开发治疗 在诸如缺氧的病理损伤期间适用的干预， 缺血和低血糖。

The adrenal steroid corticosterone is known to enhance glutamate neurotoxicity in the hippocampus. Corticosteroids are proposed to contribute to neurotoxic events such as hypoxia, ischemia and hypoglycemia by potentiating the activity of glutamate in the synapse, which ultimately results in the activation of nitric oxide synthase(NOS). However, in addition to potentiating the action of glutamate, corticosteroids may also modulate these events by regulating the expression of NOS isoforms. Accordingly, the objective of this proposal are to examine corticosteroid regulation of NOS isoforms in experimental paradigms which produce stress-induced neuronal atrophy in the hippocampus. Changes in the expression of NOS isoforms in the hippocampus will be examined by in situ hybridization histochemisty. The ability of inhibitors of NOS activity to attenuate corticosteroid mediated neuronal atrophy will also be evaluated. These studies will allow for a better understanding of the underlying molecular mechanisms through which corticosteroids produce neuronal atrophy during stress. In addition, these results could contribute to the development of therapeutic interventions applicable during such pathological insults as hypoxia, ishemia and hypoglycemia.