Neurochemical mechanism for the behavioral disturbances in the Se-deficient mice : an evaluation with in vivo microdialysis.

缺硒小鼠行为障碍的神经化学机制：体内微透析评估。

• 批准号: 08670413
• 负责人: WATANABE Chiho
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670413/
• 关键词: selenium; selenium deficiency; microdialysis; dopamine; nomifensine; dopamine transporter; open field test; mouse; マイクロダリアリシス; 脳; 線条体; オープンフィールド

We have previously reported that a prolonged Se deficiency in mice results in behavioral alteration. Elucidation of the underlying neurochemical mechanism for this behavioral effect of Se deficiency was the goal of the present study.A model for postweaning Se deficiency was developed using mice ; in this process, we have found that decrease in Se concentration was significantly more pronounced in cerebrum than in cerebellum or in brain stem. Taking this result as well as the results from preceding studies into account, we have examined the extracellular concentration (as an index of release) of dopamine (DA) in the striatum of Se-deficient mice with in vivo microdialysis. In vivo microdialysis was selected to evaluate possible neurochemical effect (s) of Se deficiency because of its direct link to behavioral output. After aporox.4 weeks on low-Se-diet regimen, the Se-deficient group was not different from the control (Se-adequate) group regarding the extracellular concentration of DA under a "basal" condition or under a depolarizing stimulus with high-K^+ perfusion. After 12 week of Se deficiency, the deficient group showed a DA increase upon high-K^+ perfusion, which was significantly greater than the one observed in the control group. To determine whether this alteration in the DA metabolism is related with any behavioral effects of Se deficiency, an open-field test with or without nomifensine (NOM), a selective inhibitor for the DA transporter, was conducted. After 14 week of Se deficiency, the activity in the open-field apparatus was significantly greater in the Se-deficient group than in the control group. Prior administration of NOM increased the activity of both the groups, the effect being slightly exaggerated in the deficient group. In addition, this dose of NOM increased extracellular DA in the striatum. Taken together, these results suggested that the Se deficiency increased the open-field activity by an enhanced DA release in the striatum.

我们之前已经报道过，小鼠长期缺硒会导致行为改变。本研究的目的是阐明缺硒行为效应的神经化学机制。利用小鼠建立断奶后缺硒动物模型；在此过程中，我们发现大脑中的Se浓度下降明显高于小脑或脑干。考虑到这一结果以及以前的研究结果，我们用体内微透析检测了缺硒小鼠纹状体内多巴胺(DA)的胞外浓度(作为释放的指标)。在体微透析被用来评估硒缺乏可能的神经化学效应(S)，因为它与行为输出直接相关。低硒饮食4周后，在“基础”状态和高K+灌流去极化刺激条件下，缺硒组细胞外DA浓度与对照组无明显差异。缺硒12周后，缺硒组高K+灌流时DA升高，明显高于对照组。为了确定DA代谢的这种改变是否与缺硒的任何行为效应有关，我们进行了一项旷场实验，包括使用或不使用DA转运蛋白的选择性抑制剂诺米芬辛(Nom)。缺硒14周后，缺硒组大鼠旷场器官的活性显著高于对照组。预先给予NOM增加了两组的活动，这种影响在缺陷组略有夸大。此外，此剂量的NOM可增加纹状体细胞外DA的含量。综上所述，这些结果表明，缺硒通过增加纹状体DA的释放来增加开野活动。

项目成果

C.Watanabe et al.: "Defeciency of selenium enhances the K± induced veleaue of dopamine in the striature of mice." Neuroscience Letters. 236. 49-52 (1997)

C. Watanabe 等人：“硒缺乏会增强小鼠纹状体中 K+ 诱导的多巴胺含量。” 神经科学快报 236. 49-52 (1997)

C.Watanabe et al.: "Tissue-specific modification of the selenium concentration by acute and chronic dexamethazone administration in mice." British Journal of Nutrition. vol.78. 501-509 (1997)

C.Watanabe 等人：“通过对小鼠进行急性和慢性地塞米松给药，对硒浓度进行组织特异性改变。”

C.Watanabe, et al.: "Tissue-specific modification of the selenium coucentration by acute and chronic deiamethazone adoministration in mice." British Journal of Nutrition. 78. 501-509 (1997)

C.Watanabe 等人：“通过对小鼠进行急性和慢性地亚米松给药对硒浓度进行组织特异性改变。”

C.Watanabe, et al.: "Deficiency of selenium enhauces the K^+_- induced release of dopamine in the striatum of mice" Neuroscience Letters. 236. 49-52 (1997)

C.Watanabe 等人：“硒缺乏会增强小鼠纹状体中 K^_- 诱导的多巴胺释放”《神经科学快报》。

渡辺ら: "セレン欠乏マウスの線条体ドパミン放出" 日本衛生学雑誌. (印刷中). (1997)

Watanabe 等人：“缺硒小鼠的纹状体多巴胺释放”，《日本卫生杂志》（出版中）。