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

为了研究衰老对应激诱导的大鼠脑中去甲肾上腺素释放增加的影响，对两种不同年龄的雄性Wistar大鼠（9周龄和12月龄）进行了研究。用戊巴比妥麻醉大鼠，并将U形透析探针植入下丘脑前部。所有实验均在手术后24小时进行。用人工脑脊液以2 ml/min的恒定流速连续灌注微透析探针。在应激暴露前60 min、应激暴露期间和应激释放后80 min收集微透析样品（40 μl/20 min）。采用了两种应力范例，即，用金属丝网固定应激和心理应激，其中大鼠暴露于其他电击大鼠所示的情绪反应，如挣扎、发声、排便和跳跃，但它们自己没有接受电击。急性期 ...更多信息 实验中，制动应激和心理应激分别持续120 min和20 min。在慢性实验中，大鼠每天暴露于制动应激120 min，持续7 d。采用高效液相色谱-电化学检测法测定去甲肾上腺素的含量。年轻（9周龄）和老年（12月龄）大鼠的基础去甲肾上腺素水平无显著差异。急性心理应激和束缚应激均能显著增加青年和老年大鼠下丘脑前部去甲肾上腺素的释放，但青年大鼠的增加量显著高于老年大鼠。提示老年大鼠去甲肾上腺素能神经元对急性应激的反应减弱。此外，由固定应激引起的去甲肾上腺素释放的增加程度是由心理应激引起的去甲肾上腺素释放的增加程度的约两倍，这表明固定应激是比心理应激更强烈的应激源。在幼鼠反复制动应激7天后，制动应激2小时或心理应激20分钟所引起的去甲肾上腺素释放量均显著低于未暴露于应激的幼鼠。相反，在老年大鼠先前暴露于反复制动应力7天，去甲肾上腺素释放引起的心理应激进一步增加，然而，去甲肾上腺素释放制动应力是几乎相同的幼稚大鼠暴露于压力。这些结果表明，青年大鼠能够适应重复应激，而老年大鼠难以适应重复应激。在下丘脑室旁核、蓝斑、杏仁中央核、内侧前额叶皮质和丘脑室旁核等脑区均观察到Fos表达，提示这些脑区在束缚应激时被激活，但在青年和老年大鼠之间无差异。在重复应力或不同应力的情况下，还需要进一步研究。少

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》。

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)。

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 stidies."European Journal of Pharmacology. 405. 397-406 (2000)

Tanaka M、Yoshida M、Emoto H 和 Ishii H：“下丘脑、杏仁核和蓝斑中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》。