title: Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2.
abstract: 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.
authors.affiliation: School of Pharmacy, University of Camerino, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Carloni
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nasuti
authors.forename: Donatella
authors.initials: D
authors.lastname: Fedeli
authors.forename: Maura
authors.initials: M
authors.lastname: Montani
authors.forename: M S Dhivya
authors.initials: MS
authors.lastname: Vadhana
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
authors.forename: Rosita
authors.initials: R
authors.lastname: Gabbianelli
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007306:Insecticides / Q000633:toxicity; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000096:biosynthesis*; D026023:Permethrin / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D007306:Insecticides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D026023:Permethrin