Early life permethrin treatment induces neurodegeneration in adult and old rats.

Neonatal exposure to permethrin induces long-lasting effects after developmental exposure giving changes in striatal monoamine level and increased oxidative stress (1). In the present study, pup rats have been exposed to permethrin treatment by gavage (1/50 LD50, from 6th to 21st day of life). Biochemical and molecular biology studies have been performed in order to investigate in adult (300 days) and old rats (495 days) an eventual neurodegeneration in different brain areas, striatum, prefrontal cortex and hippocampus. In adult rats Nurr1, mRNA and protein expression, as well as calcium and NO levels are decreased in striatum. Moreover, the pesticide induces an imbalance in glutamate, calcium and NO in hippocampus. Low calcium concentrations in leukocytes and in plasma were observed, while increased NO and decreased SOD plasma levels were measured. In old rats in addition to Nurr 1 we investigated also NFkB and Nrf2 genes and their protein levels; these genes resulted differently modified in striatum, hippocampus and cerebellum of treated group. Moreover Nurr1 and NF-kB activation was correlated with higher calcium level in striatum, prefrontal cortex and cerebellum, while Nrf2 resulted increased only in cerebellum. In old rats, NO and calcium c levels showed similar results of adult rats except for the unchanged SOD level.