Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2

• Early life permethrin treatment induces long-lasting effects in brain.
• Permethrin exposure decreases Nurr1 gene expression in striatum of old rats.
• Nurr1 gene expression increases in hippocampus and cerebellum of treated rats.
• NF-kB p65 and Nrf-2 gene expression increases in cerebellum of treated rats
• Permethrin increases NF-kB p65 in cerebellum and cortex while reduces in hippocampus.

Pesticide exposure during brain development represents an important risk factor for the onset of brain-aging processes. Here, the impact of permethrin administered to rats from 6th to 21st day of life, at a dose near to “no observed adverse effect level” (NOAEL), was studied when animals reached 500 day-old. The permethrin treatment induced a decrease in Nurr1 gene expression in striatum, an increase in hippocampus and cerebellum, while the protein level changed only in striatum where it was increased. NF-kB p65 gene expression was increased in cerebellum, while its protein level augmented in cerebellum and in prefrontal cortex and decreased in hippocampus of treated rats compared to control ones. Nrf-2 gene expression resulted significantly higher only in cerebellum of treated animals. The results suggest that early life permethrin treatment induces long-lasting effects leading to dopaminergic neuronal disorders, monitored by Nurr1 alteration. Moreover the impairment of NF-kB and Nrf-2, important for the balance between pro- and anti-inflammatory systems, confirms that the neonatal permethrin treatment can influence genes involved with the onset of brain-ageing processes.