López-Figueroa M O, Itoi K, Watson S J
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
Neuroscience. 1998 Nov;87(2):439-46. doi: 10.1016/s0306-4522(98)00075-x.
Nitric oxide and glucocorticoids have been implicated in learning and memory, as well as in regulation of the stress response. By use of the in situ hybridization technique, we examined the role of glucocorticoids in the regulation of nitric oxide synthase messenger RNA in the hippocampus. In control animals, nitric oxide synthase subtype I (neuronal) messenger RNA was expressed in the CA1, CA3 and dentate gyrus of the hippocampus. Nitric oxide synthase subtype I expression was almost absent in CA2 pyramidal neurons. Neither subtype II (immunological) nor subtype III (endothelial) nitric oxide synthase messenger RNAs were observed in neurons of the hippocampal subfields. Bilateral removal of the adrenal glands resulted in a significant increase in nitric oxide synthase subtype I messenger RNA expression in the CA1 and CA3 pyramidal neurons and in granular cells of the dentate gyrus. To a lesser degree, the nitric oxide synthase subtype I messenger RNA signal was increased in CA2 pyramidal neurons. Daily administration of glucocorticoids for one week attenuated the adrenalectomy-induced increased level of expression of the messenger RNA encoding nitric oxide synthase subtype I in all areas studied. Because adrenalectomy, which suppresses the production of glucocorticoids, increases nitric oxide synthase expression, and replacement of adrenalectomized animals with glucocorticoids restores the basal levels of nitric oxide synthase subtype I expression, our results demonstrate an up-regulation of nitric oxide synthase subtype I messenger RNA in the absence of glucocorticoids in the hippocampus. The present findings suggest an involvement of the stress axis in the regulation of the synaptic plasticity process mediated by nitric oxide in the hippocampus.
一氧化氮和糖皮质激素与学习和记忆以及应激反应的调节有关。通过使用原位杂交技术，我们研究了糖皮质激素在海马体中一氧化氮合酶信使核糖核酸调节中的作用。在对照动物中，一氧化氮合酶I型（神经元型）信使核糖核酸在海马体的CA1、CA3和齿状回中表达。CA2锥体神经元中几乎不存在一氧化氮合酶I型表达。在海马体亚区的神经元中未观察到II型（免疫型）和III型（内皮型）一氧化氮合酶信使核糖核酸。双侧肾上腺切除导致CA1和CA3锥体神经元以及齿状回颗粒细胞中一氧化氮合酶I型信使核糖核酸表达显著增加。在较小程度上，CA2锥体神经元中一氧化氮合酶I型信使核糖核酸信号也增加。连续一周每日给予糖皮质激素可减弱肾上腺切除诱导的所有研究区域中编码一氧化氮合酶I型信使核糖核酸表达水平的升高。由于抑制糖皮质激素产生的肾上腺切除会增加一氧化氮合酶表达，而用糖皮质激素替代肾上腺切除的动物可恢复一氧化氮合酶I型表达的基础水平，我们的结果表明海马体中在缺乏糖皮质激素的情况下一氧化氮合酶I型信使核糖核酸上调。目前的研究结果表明应激轴参与了海马体中由一氧化氮介导的突触可塑性过程的调节。
