title: The impact of early life permethrin exposure on development of neurodegeneration in adulthood.
abstract: Early life environmental exposure to pesticides could play a critical role in the onset of age-related diseases. The present study aims to evaluate in brain, plasma and leukocytes of 300 day-old rats, the effect of a low dose of the insecticide permethrin administered during early life (1/50 LD(50), from 6th to 21st day of life). The outcomes show that 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. The results suggest that permethrin intake at a dose close to the NOAEL (25 mg/kg) during the perinatal period can interact with Nurr1 by reducing its expression on striatum nucleus. Consequently, the maintenance of dopaminergic neurons as well as Nurr1 inhibitory effect on the production of proinflammatory mediators fails. The changes in biological markers found in our animal model could represent the basis to study neurodegenerative diseases whose development depends on individual gene signature and life style.
authors: School of Pharmacy, University of Camerino, Italy.
authors: Manuel
authors: M
authors: Carloni
authors: Cinzia
authors: C
authors: Nasuti
authors: Donatella
authors: D
authors: Fedeli
authors: Maura
authors: M
authors: Montani
authors: Augusto
authors: A
authors: Amici
authors: M S Dhivya
authors: MS
authors: Vadhana
authors: Rosita
authors: R
authors: Gabbianelli
mesh_terms: D000199:Actins / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced*; D009569:Nitric Oxide / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D026023:Permethrin / Q000633:toxicity*; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000199:Actins; D007306:Insecticides; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D009569:Nitric Oxide; D018698:Glutamic Acid; D026023:Permethrin; D012313:RNA; D013482:Superoxide Dismutase; D002118:Calcium