title: Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats.
abstract: Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 μg/L and it was completely eliminated after 96 h.
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy. cinzia.nasuti@unicam.it
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nasuti
authors.forename: Manuel
authors.initials: M
authors.lastname: Carloni
authors.forename: Donatella
authors.initials: D
authors.lastname: Fedeli
authors.forename: Rosita
authors.initials: R
authors.lastname: Gabbianelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.forename: Cerasa Laura
authors.initials: CL
authors.lastname: Serafina
authors.forename: Isabel
authors.initials: I
authors.lastname: Silva
authors.forename: Valentina
authors.initials: V
authors.lastname: Domingues
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000367:Age Factors; D000818:Animals; D001565:Benzoates / Q000652:urine; D003072:Cognition Disorders / Q000139:chemically induced*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D026023:Permethrin / Q000008:administration & dosage / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
chemical_list: D001565:Benzoates; D007306:Insecticides; D012701:Serotonin; D026023:Permethrin; C017618:3-phenoxybenzoic acid; D004298:Dopamine; D009638:Norepinephrine