www.elsevier.com/locate/brainres Available online at www.sciencedirect.com Research Report Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2 Manuel Carloni a,1 , Cinzia Nasuti a,1 , Donatella Fedeli a,1 , Maura Montani b , M.S Dhivya Vadhana c , Augusto Amici b , Rosita Gabbianelli a,n a School of Pharmacy, University of Camerino, Italy b School of Biosciences and Biotechnology, University of Camerino, Italy c School of Advanced Studies, University of Camerino, Italy article info Article history: Accepted 29 March 2013 Available online 6 April 2013 Keywords: Rat Early-life-permethrin-treatment Brain Nurr1 NF-kB 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. More- over 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. & 2013 Elsevier B.V. All rights reserved. 1. Introduction Ageing is a physiological change characterized by a decline in protein homeostasis and accumulation of macromolecular damage in different organs as well as in brain. Genetic and environmental factors, life style, metabolic processes, as well as reactive oxygen species have an impact on the neurode- generative process (Parrón et al., 2011; Zhang et al., 2006). Moreover on the development of different types of neurode- generation (i.e. Alzheimer disease (AD), Parkinson’s diseases (PD) etc.) that characterize ageing processes, the stochastic event is the most determinant, because it influences both gene expression and epigenetic pathways, and could partially explain the reported variability and random fluctuations of individual gene expression in genetically identical organisms (Raj and Van Oudenaarden, 2008). Studies on neurodegenerative diseases are dominated by research performed in model systems, such as yeast, worms, flies and genetically modified mice because animal models permit the assessment of markers of neurodegeneration in 0006-8993/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.brainres.2013.03.048 n Correspondence to: School of Pharmacy, Via Gentile III da Varano, UNICAM, 62032 Camerino, MC, Italy. Fax: +39 0737 403290. E-mail address: rosita.gabbianelli@unicam.it (R. Gabbianelli). 1 These authors contributed equally to the study brainresearch 1515 (2013)19–28