APPENDIX II-AL:  Imamura, et al, Neonatal exposure of newborn mice to pyrethroid (permethrin) represses activity-dependent c-fos mRNA expression in cerebellum , Archives of Toxicology, v. 76, no. 7 (July 2002) 392-397.


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


Archives of Toxicology


Springer Berlin / Heidelberg


0340-5761 (Print) 1432-0738 (Online)


Volume 76, Number 7 / July, 2002


Molecular Toxicology







Lisa Imamura, Hiroshi Hasegawa, Kaori Kurashina, Tomoya Matsuno, Masaaki Tsuda

1Toyama Medical and Pharmaceutical University, Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Sugitani 2630, Toyama 930-0194, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Shibuya 3-13-11, Tokyo 150-0002, Japan


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 #-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.