Exposure to pesticides can induce neurobehavioral effects in rodents, as well as in other mammals, including humans. However, the effects of the toxicity of pesticides on the central nervous system (CNS) remain largely unclear. The expression of the activity-regulated cytoskeleton-associated protein gene (Arc) is induced in a neuronal-activity-dependent manner and is implicated in synaptic and experience-dependent plasticity. We previously developed Arc-promoter-driven luciferase transgenic (Tg) mouse strains to monitor the neuronal-activity-dependent gene expression under physiological and pathological conditions in vivo. In this study, we examined the effect of acute administration of four different pesticides (deltamethrin, glufosinate, methylcarbaryl, and imidacloprid) on neuronal activity using Arc-Luc Tg mice. The change in the bioluminescence signal in mouse brain upon treatment with deltamethrin and glufosinate occurred more slowly than that of kainic acid, a potent neuroexcitatory amino acid agonist. These two pesticides also caused convulsive responses in adult Arc-Luc Tg mice. In the case of glufosinate, we detected the long-term upregulation of bioluminescence signal intensity of Arc-Luc over 24 h after the treatment. Furthermore, we observed greater changes of bioluminescence signal in adults than in juveniles, and a lower incidence of convulsions at the juvenile stage. In contrast to the acute treatment, we detected a decrease of bioluminescence signal after low-dose chronic treatment with glufosinate, without neuronal overexcitation. From these results, we suggest that Arc-Luc Tg mice are useful for assessing the acute and chronic effects of pesticides on the CNS.

中文翻译：

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急性和慢性暴露于农药下的小鼠大脑中Arc表达的生物发光成像。

接触杀虫剂可在啮齿动物以及包括人在内的其他哺乳动物中诱发神经行为。但是，农药对中枢神经系统（CNS）的毒性影响尚不清楚。活性调节的细胞骨架相关蛋白基因（Arc）的表达以神经元活性依赖性的方式被诱导，并且牵涉到突触和经验依赖性的可塑性。我们以前开发了弧启动子驱动的荧光素酶转基因（Tg）小鼠品系，以监测体内生理和病理条件下神经元活性依赖性基因的表达。在这项研究中，我们检查了使用Arc-Luc Tg小鼠急性施用四种不同的农药（溴氰菊酯，草铵膦，甲基甲萘威和吡虫啉）对神经元活性的影响。用溴氰菊酯和草铵膦处理后，小鼠大脑中生物发光信号的变化发生的速度比海藻酸（一种有效的神经兴奋性氨基酸激动剂）的发生更慢。这两种农药还引起成年Arc-Luc Tg小鼠惊厥反应。在草铵膦的情况下，我们检测到治疗后24小时内Arc-Luc的生物发光信号强度长期上调。此外，我们观察到成年人中生物发光信号的变化要比青少年更大，而在青少年期惊厥的发生率也较低。与急性治疗相反，我们发现在低剂量慢性用草铵膦治疗后，没有神经元过度兴奋，生物发光信号有所减少。根据这些结果，