Effect of nitric oxide on release of neurotransmitters in the brain

一氧化氮对大脑神经递质释放的影响

• 批准号: 10670917
• 负责人: SUZUKI Eiji
• 金额: $ 2.05万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670917/
• 关键词: nitric oxide; immobilization stress; nitric oxide synthase; nitrite; nitrate; brain; rat; うつ病

At first, we investigated whether nitric oxide synthase (NOS) gene was induced by immobilization stress (IMS) in rat hypothalamus, hippocampus, cerebral cortex, and cerebellum, using reverse transcription-polymerase chain reaction. Animals were treated in accordance with the National Institutes of Health guide for the care and use of Laboratory animals. Immobilization stress induced the expression of iNOS mRNA in every brain region examined with a peak around 30 or 60 min. This result suggests that, since iNOS is tanscriptionally-regulated enzyme, it is induced by stress exposure in the brain.The objection of the second experiment was that we investigated whether nitric oxide (NO) levels changed after the initiation of IMS in the hypothalamus of free-moving rats, Rats were anesthetized and inplanted a guide canule in the hypothalamus. After 1 week, a microdialysis probe was inserted into the hypothalamus and was perfused with Hanks's solution. The dialysate were injected in an automate … More d NO detector-hyperformance-liquid-chromatography system (ENO-10, Eicom, Kyoto, Japan) directly. Four or more hours later, assays of NOィイD3-(/)2ィエD3 and NOィイD3-(/)3ィエD3 levels were started, and then the basal levels were measured for two or more hours. Between 40 and 120 min after starting of iMS, NOィイD3-(/)2ィエD3 and NOィイD3-(/)3ィエD3 levels increased significantly.Finally, we investigated plasma NOィイD3-(/)2ィエD3 and NOィイD3-(/)3ィエD3 levels in untreated 17 patients with depressive episodes, untreated seven patients with anxiety disorders, and 12 healthy controls. Written informed consent was obtained from each individual.No significant difference was found in plasma nitrite levels among the groups. Plasma NOィイD3-(/)3ィエD3 levels in depressed patients were significantly higher than those in controls or patients with anxiety disorders (Scheffe's F test, P<0.05, figure). Moreover, in patients with depressive episodes, nitrate levels significantly decreased, approximately to control levels, after recovery (Wilcoxon signed-ranks test, P<0.01, figure).Unclear remains the source of the surplus production of nitric oxide in patients with depressive episodes. However, measurement of plasma nitrate levels might be useful in the differential diagnosis of affective disorders versus anxiety disorders. Less

首先，我们研究了是否一氧化氮合酶（NOS）基因的诱导，在大鼠下丘脑，海马，大脑皮层和小脑的制动应激（IMS），采用逆转录-聚合酶链反应。根据美国国立卫生研究院实验室动物护理和使用指南对动物进行处理。固定应激诱导了各脑区iNOSmRNA的表达，在30或60 min左右达到峰值。这一结果表明，由于iNOSmRNA是转录调节酶，因此它是由脑内的应激暴露诱导的。第二个实验的目的是研究自由活动大鼠下丘脑中一氧化氮（NO）水平在IMS启动后是否发生变化，将大鼠麻醉并在下丘脑中植入引导导管。1周后，将微透析探针插入下丘脑，并用Hanks溶液灌注。透析液被注入自动 ...更多信息 d直接使用NO检测器-高效液相色谱系统（ENO-10，Eicom，京都，日本）。4小时或更长时间后，开始测定NO受体D3-（/）2 β D3和NO受体D3-（/）3 β D3水平，然后测量基础水平2小时或更长时间。在开始iMS后的40和120 min之间，NO-2-D3和NO-3-D3水平显著升高。最后，我们研究了17例未经治疗的抑郁发作患者、7例未经治疗的焦虑障碍患者和12例健康对照者的血浆NO-2-D3和NO-3-D3水平。各组血浆亚硝酸盐水平无显著性差异。抑郁症患者血浆NO-β_3D_3-（/）_3水平显著高于正常对照组和焦虑症患者（Scheffe’s F检验，P<0.05，图）。此外，抑郁发作患者的硝酸盐水平在恢复后显著下降，接近对照水平（Wilcoxon符号秩检验，P<0.01，图）。抑郁发作患者过量产生一氧化氮的来源尚不清楚。然而，血浆硝酸盐水平的测量可能是有用的情感障碍与焦虑症的鉴别诊断。少

项目成果

Suzuki, E., Shintani, F., Kanba S., Asai M., Nakaki, T.: "Immobilization stress induces iNOS gene expression in the rat brain"Neurochemical Res.. 24. 141 (1999)

Suzuki, E.、Shintani, F.、Kanba S.、Asai M.、Nakaki, T.：“固定应激诱导大鼠脑中 iNOS 基因表达”神经化学研究 24. 141 (1999)

Nakaki, T., Fujii, T., Suzuki, E., and Shintani, F.: "Endothelium-independent and -dependent vasoactivity of 6-nitronrepinephrine"European Journal of Pharmacology. 357. 193-197 (1998)

Nakaki, T.、Fujii, T.、Suzuki, E. 和 Shintani, F.：“6-硝基肾上腺素的内皮依赖性和依赖性血管活性”欧洲药理学杂志。

Suzuki, E., Yagi, G., Nakaki, T., Kanba, S., and Asai, M.: "Elevated plasma nitrate levels in depressive states"Journal of Affective Disorders. in press).

Suzuki, E.、Yagi, G.、Nakaki, T.、Kanba, S. 和 Asai, M.：“抑郁状态下血浆硝酸盐水平升高”情感障碍杂志。

Nakaki T,Fujii T,Suzuki E,Shintani F: "Endothelium-independent and-dependent vasoactivify of 6-nitronor-epinephrine"Eur.J.Pharmacology. 357. 193-197 (1998)

Nakaki T、Fujii T、Suzuki E、Shintani F：“6-硝基去甲肾上腺素的内皮依赖性和依赖性血管活化”Eur.J.药理学。

Suzuki, E., Shintani, F., Kanba, S., Asai, M., Nakaki, T.: "Immobilization stress induces iNOS gene expression in the rat brain"Neurochemical Research. Vol.24. 141 (1999)

Suzuki, E.、Shintani, F.、Kanba, S.、Asai, M.、Nakaki, T.：“固定应激诱导大鼠大脑中 iNOS 基因表达”神经化学研究。