title: Early life exposure to permethrin: a progressive animal model of Parkinson's disease.
abstract: BACKGROUND
  Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life.
  
  
  METHODS
  The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only.
  
  
  RESULTS
  At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa.
  
  
  CONCLUSIONS
  The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease.
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy. Electronic address: cinzia.nasuti@unicam.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nasuti
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Brunori
authors.affiliation: Department of Pharmacy, University of "G. D'Annunzio" Chieti-Pescara, Via dei Vestini, 66100 Chieti, CH, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Eusepi
authors.affiliation: Department of Pharmacy, University of "G. D'Annunzio" Chieti-Pescara, Via dei Vestini, 66100 Chieti, CH, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Marinelli
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
authors.affiliation: School of Pharmacy, Molecular Biology Unit, University of Camerino, Via Gentile III da Varano, 62032 Camerino, MC, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Gabbianelli
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D026023:Permethrin / Q000633:toxicity*; D017208:Rats, Wistar; D045442:Rotarod Performance Test
chemical_list: D026023:Permethrin; D004298:Dopamine
keywords: Animal model; Behavior; Dopamine; L-Dopa; Method; Motor disabilities; Parkinson; Permethrin; Permethrin (PubChem CID:40326); Substantia nigra