Characteristics of the neurotransmitter release caused by stress in aged rats.

老年大鼠应激引起的神经递质释放特征。

• 批准号: 11670108
• 负责人: TANAKA Masatoshi
• 金额: $ 1.92万
• 依托单位: Kurume University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670108/
• 关键词: stress; aging; brain; rat; noradrenaline; Fos protein; microdialysis; 老化; Fosタンパク; 視床下部

In order to investigate the effects of aging on stress-induced increases in noradrenaline release in the rat brain, the two different aged male Wistar rats, 9 week and 12 month old, were subjected to the study. The rats were anesthetized with pentobarbital and implanted with a U-shaped dialysis probe into the anterior hypothalamus. All the experiments were carried out 24 hrs after the operation. The microdialysis probe was continuously perfused at a constant flow rate of 2 ml/min with an artificial cerebrospinal fluid. The microdialysis samples (40 μl/20 min) were collected for 60 min before stress exposure, then during stress exposure and for 80 min after release from stress. The two stress paradigms were employed, i.e., immobilization stress with a wire mesh and psychlogical stress where the rats were exposed to emotional responses such as struggling, vocalization, defecation and jumping shown by other electrically-shoked rats but received no electric shock by themselves. In acute ex … More periments, immobilization stress and psychological stress were continued for 120 min and 20 min, respectively. In the chronic experiments, the rats were exposed to immobilization stress for 120 min daily for 7 days. The noradrenaline contenst were determined by high liquid chromatography with electrochemical detection. Basal noradrenaline levels were not significantly different between young (9 week old) and aged (12 month old) rats. Although acute psychological stress and immobilization stress significantly increased noradrenaline release in the anterior hypothalamus in young rats and aged rats, the increase in young rats was significantly higher than that in aged rats. This finding suggested that the noradrenergic neuronal response to acute stress was attenuated in aged rats. Moreover, the degree of increases in noradrenaline release caused by immobilization stress is about two times greater than that induced by psychological stress, suggesting that the immobilization stress is a more intense stressor than is psychological stress. In young rats previously exposed to repeated immobilization stresses for 7 days, noradrenaline release elicited by 2 hrs of immobilizatioin stress or 20 min of psychological stress was significantly decreased as compared to that in naive rats exposed to stress. In contrast, in aged rats previously exposed to repeated immobilization stresses for 7 days, noradrenaline release elicited by psychological stress was further increased, however, noradrenaline release by immobilization stress was almost the same in naive rats exposed to stress. These results suggest that young rats can adapt to repeated stress, however, it is difficult for aged rats to adapt to repeated stressors.Further we investigated immunohistochemically Fos-expression in the brain in young and aged rats exposed to stress. Fos-expression was observed in such brain regions as the paraventricular nucleus of the hypothalamus, locus coeruleus, the central nucleus of the amygdala, the medial prefrontal cortex and the paraventricular nucleus of the thalamus, suggesting that these brain regions were activated by immobilization stress, however, no difference between the young and aged rats was obatined. Further studise where such as repeated stresses or different stresses are employed should be needed. Less

为了研究衰老对大鼠大脑去甲肾上腺素释放的压力诱导的升高的影响，对两名不同的老年男性Wistar大鼠（9周零12个月）都受到了研究。用戊巴比妥麻醉大鼠，并用U形透析探针植入前下丘脑。手术后24小时进行所有实验。微透析探针以人工脑脊液的恒定流速为2 ml/min，以2 ml/min的恒定流速进行灌注。在压力暴露之前，在压力暴露期间和从应力中释放后80分钟，收集了微透析样品（40μL/20分钟）60分钟。采用了两个应力范式，即用金属丝网和心理压力固定应力，使大鼠暴露于情绪反应中，例如挣扎，发声，排便和其他电动大鼠所显示的，但没有收到电动冲击。在急性的前…更多的内部，固定应力和心理压力分别持续了120分钟和20分钟。在慢性实验中，将大鼠暴露于固定应力，每天120分钟，持续7天。去甲肾上腺素的含量通过高液相色谱法确定，并具有电化学检测。尽管急性心理压力和固定压力显着增加了年轻大鼠和年龄大鼠的下丘脑中肾上腺素的释放，但基底去甲肾上腺素水平并不是，但年轻大鼠的增加显着高于年龄大鼠。这一发现表明，在老年大鼠中，甲状腺素能神经元对急性应激的反应减弱。此外，由固定压力引起的去甲肾上腺素释放的增加程度大约是心理压力引起的两倍，这表明固定压力是一种比心理压力更强烈的压力。在以前暴露于重复固定应力7天的年轻大鼠中，与暴露于压力的天真大鼠相比，与固定压力的2小时或20分钟的心理压力相比，去甲肾上腺素释放或心理压力20分钟得到了显着改善。相反，在先前暴露于重复固定应力的年龄大鼠中，心理压力引起的去甲肾上腺素释放进一步增加，但是，暴露于压力的天真大鼠中，抗抑制应激释放几乎是相同的。这些结果表明，年轻的大鼠可以适应反复的压力，但是，老年大鼠很难适应重复的压力。库尔瑟研究了暴露于压力的年轻大鼠和年龄大鼠的大脑中的免疫组织化学表达。在这样的大脑区域中观察到FOS表达，例如下丘脑的旁脑核核，基因座核，杏仁核的中央核核，中位前额叶皮层和丘脑的副核核核素，这些丘脑的核心是未经群体激活了这些大脑区域，这表明这些大脑区域被激活了，并不是在未来的压力激活的，并且曾在年轻人之间呈现。需要雇用诸如重复应力或不同应力之类的更多工作室。较少的

项目成果

呉 英良,吉田正美,江本浩幸,石井秀夫,山岡俊彦,長谷川雅一,田中正敏: "W-プローブを用いた脳内マイクロダイアリーシス法の有用性の検討"久留米医学会雑誌. 62. 185-191 (1999)

Eiyoshi Kure、Masami Yoshida、Hiroyuki Emoto、Hideo Ishii、Toshihiko Yamaoka、Masakazu Hasekawa、Masatoshi Tanaka：“使用 W 探针的脑内微透析方法的有效性检查”久留米医学会杂志 62. 185 -191 (1999)。

Wu L-Y,Yoshida M,Emoto Y and Tanaka M: "Psychological stress selectively increases extracellualr dopamine in the 'shell', but not in the 'core' of the rat nucleus accumbens, a novel dual-needle probe simultaneous microdialysis study."Neuroscience Letters.

Wu L-Y、Yoshida M、Emoto Y 和 Tanaka M：“心理应激选择性增加大鼠伏隔核‘壳’中的细胞外多巴胺，但不会增加大鼠伏隔核‘核心’的细胞外多巴胺，这是一项新型双针探针同时微透析研究。”神经科学

Tanaka M, Yoshida M, Emoto H and Ishii H: "Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety : basic studies."European Journal of Pharmacology. 405. 397-406 (2000)

Tanaka M、Yoshida M、Emoto H 和 Ishii H：“下丘脑、杏仁核和蓝斑的去甲肾上腺素系统参与焦虑的激发：基础研究。”《欧洲药理学杂志》。

Wu L-Y,Yoshida M,Emoto Y and Tanaka M: "Psychological stress selectively increases extracellular dopamine in the 'Shell',but not in the 'core'of the rat nucleus accumbens.a novel dual-needle probe simultaneous microdialysis study."Neuroscience Letters. 27

Wu L-Y、Yoshida M、Emoto Y 和 Tanaka M：“心理应激选择性地增加大鼠伏隔核‘壳’中的细胞外多巴胺，但不会增加大鼠伏隔核‘核心’中的多巴胺。一项新型双针探针同时微透析研究。”神经科学

呉英良,吉田眞美,江本浩幸,石井秀夫,山岡俊彦,長谷川雅一,田中正敏: "W-プローブを用いた脳内マイクロダイアリーシス法の有用性の検討"久留米医学会雑誌. 62. 185-191 (1999)

Eiyang Wu、Mami Yoshida、Hiroyuki Emoto、Hideo Ishii、Toshihiko Yamaoka、Masakazu Hasekawa、Masatoshi Tanaka：“使用 W 探针检查脑内微透析方法的有效性”久留米医学会杂志 62. 185 -191 (1999)。