ADRENAL STEROID REGULATION OF NOS ISOFORMS

已知肾上腺类固醇皮质酮可以增强谷氨酸。 海马体的神经毒性。皮质类固醇被认为可以 会导致神经毒性事件，如缺氧、缺血和 通过增强突触中谷氨酸的活性来降低血糖， 最终导致一氧化氮合酶(NOS)的激活。 然而，除了增强谷氨酸的作用外， 皮质类固醇也可能通过调节 一氧化氮合酶亚型的表达。因此，这项提案的目标是 是为了研究皮质类固醇对实验性一氧化氮合酶亚型的调节 应激性神经细胞萎缩的研究范式 海马体。大鼠海马区一氧化氮合酶亚型表达的变化 将通过原位杂交组织化学方法进行检测。的能力 一氧化氮合酶抑制物减弱皮质类固醇介导的神经元 萎缩也将被评估。这些研究将允许更好的 对潜在的分子机制的理解 皮质类固醇在应激状态下会导致神经元萎缩。此外, 这些结果可能有助于治疗的发展。 在低氧等病理性侮辱期间适用的干预措施， 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.