Neonatal exposure of newborn mice to pyrethroid (permethrin) represses activity-dependent c-fos mRNA expression in cerebellum

Abstract.

In a previous report, we demonstrated that the exposure of cultured mouse cerebellar granule cells to permethrin, a type I pyrethroid insecticide, repressed the induction of activity-dependent c-fos and brain-derived neurotrophic factor (BDNF) gene expression, accompanying a decrease in Ca²⁺ influx into neurons. In addition, it has been suggested that some pyrethroids, including permethrin, are endocrine-modulating chemicals and accumulate in human breast milk. In this study, therefore, we investigated whether lactational exposure of newborn mice to permethrin influenced c-fos, BDNF and β-actin gene expression in the developing neonatal cerebellum. In the cerebella of control neonates, c-fos mRNA expression was characterized by a significant increase in postnatal weeks 2 and 3, followed by a marked decrease. In the cerebella of permethrin-treated neonates, the expression of c-fos mRNA was dose-dependently repressed by cis-permethrin more effectively than by trans-permethrin at postnatal week 3, without alterations in the body or cerebellum weights of neonates. In the fourth and fifth week, however, c-fos mRNA expression had decreased to the same level as that in the control and permethrin-treated neonates. A decrease in BDNF mRNA expression tended to be observed in the cerebella of newborn mice on exposure to permethrin. Thus, our results indicate that the activity-dependent gene expressions in cerebellar neuronal cells can be repressed by permethrin both in vitro and in vivo, and suggest that lactational exposure to pyrethroids might affect the postnatal development of the mammalian brain.