Bioluminescence imaging of Arc expression in mouse brain under acute and chronic exposure to pesticides

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.