Experimental study on the effects of organic solvent exposure to development of GABAergic system in juvenile rats

有机溶剂暴露对幼年大鼠GABA能系统发育影响的实验研究

• 批准号: 15590512
• 负责人: ITO Takehiko
• 金额: $ 1.79万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590512/
• 关键词: organic solvent intoxication; m-xylene; GABAergic system; immunohistochemistry; exposure system; juvenile animals; autoradiography; inhalation study; 曝露実験

1.Development of an exposure system suitable for exposing vapor of organic solvents to juvenile animals (rats) and inhalation study using the systemAn exposure system suitable for exposing vapor of organic solvents to juvenile animals was developed.The inner environment of the exposure chamber was designed for young rats. An ordinary mice cage with gas inlets and outlets was completely wrapped with a special gas-tight plastic bag, which was then used as the exposure chamber. With this system, inhalation study in three-week old rats was conducted. The protocol of the exposure was as follows : m-xylene at 250 ppm, 6 h/day for 14 consecutive days.2.Behavioral studyRotarod test was employed to see the effect of m-xylene of the development of the CNS. Generally co-ordination of the motor system is assessed with this test. Exposed rats showed better coordination than controls, and further study is warranted to explain the unexpected results.3.Histological studyBrain sections were made after the series of exposures. The section was stained using Luxol Fast Blue and Cresyl Violet double stain, to see possible lesions involving myelin. No significant change was observed. Immunohistochemical studies using anti-glutamate decarboxylase antibody and anti-GABA_A receptor alpha 6 subunit antibody were done, but no significant change was pointed out.Receptor binding autoradiography using [^3H]Ro15-4513 was performed. The distribution of the binding was identical to that of signals in immunostain of GABA_A receptor alpha 6 subunit. No significant change was observed.The present results suggested that there may be some significant change in locomotor function with this exposure protocol. A study in catecholaminergic and/or serotonergic system should be included along with that in GABAergic systems in the future studies.

1.一种适用于幼龄动物（大鼠）暴露有机溶剂蒸气的暴露系统的研制及其吸入研究本文研制了一种适用于幼龄动物（大鼠）暴露有机溶剂蒸气的暴露系统，暴露舱内环境设计为幼龄大鼠。将一个带有进气口和出气口的普通小鼠笼用一个特殊的气密塑料袋完全包裹起来，然后将其用作暴露室。利用该系统，在三周龄大鼠中进行吸入研究。实验方案为：间二甲苯250 ppm，6 h/d，连续暴露14 d。2.行为学研究采用转棒实验观察间二甲苯对中枢神经系统发育的影响。一般来说，运动系统的协调性通过该测试进行评估。暴露组大鼠的协调能力明显优于对照组，这一结果有待进一步研究。3.组织学研究使用Luxol Fast Blue和Cresyl Violet双重染色对切片进行染色，以查看涉及髓鞘的可能病变。未观察到显著变化。用抗谷氨酸脱羧酶抗体和抗GABA_A受体α 6亚单位抗体进行免疫组织化学研究，但未发现明显变化，用[^3H] Ro 15 -4513进行受体结合放射自显影。结合信号的分布与GABA_A受体α 6亚基免疫染色信号的分布一致。本研究结果提示，在此暴露方案下，运动功能可能有一些显著的变化。在未来的研究中，应沿着对GABA能系统的研究，包括对儿茶酚胺能和/或多巴胺能系统的研究。