title: Developmental pyrethroid exposure causes long-term decreases of neuronal sodium channel expression.
abstract: Pyrethroid insecticide use has increased over recent years because of their low to moderate acute toxicity in mammals. However, there is increasing concern over the potential detrimental effects of pyrethroids on developing animals. Most recently, we have shown that developmental exposure to deltamethrin results in long-term neurobehavioral effects. Pyrethroids exert their toxicity by acting on the voltage-gated sodium channel (Nav), delaying channel inactivation and causing hyperexcitability in the nervous system. Previous in vitro studies found that exposure to agents that increase Na+influx, including deltamethrin decreased NavmRNA expression. However, it is unknown whether this occurs in vivo. To determine whether developmental pyrethroid exposure decreases NavmRNA expression, pregnant mice were exposed to the pyrethroid deltamethrin (0 or 3mg/kg) every three days throughout gestation and lactation. NavmRNA expression was measured in the striatum and cortex of the offspring at 10-11 months of age, a time at which behavioral abnormalities were still observed. Developmental exposure to deltamethrin decreased expression of NavmRNA in a region- and isoform-specific fashion by 24-50%. Deltamethrin exposure also resulted in the persistent down-regulation of brain-derived neurotrophic factor (Bdnf) in the striatum by 66% but not in the cortex, suggesting a plausible mechanism for some of the associated behavioral effects observed previously. Taken together these data suggest that developmental deltamethrin exposure results in persistent deficits in Navand BDNF mRNA expression that may contribute to long-term behavioral deficits.
authors.affiliation: Environmental and Occupational Health Sciences Institute and Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Magby
authors.affiliation: Environmental and Occupational Health Sciences Institute and Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA; Northeast Ohio Medical University Department of Pharmaceutical Sciences, Rootstown, OH 44272, USA. Electronic address: jrichardson@neomed.edu.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Richardson
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011722:Pyrethrins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D012333:RNA, Messenger; D061566:Voltage-Gated Sodium Channels; C017180:decamethrin
keywords: BDNF; Deltamethrin; Neurodevelopmental; Pyrethroid; Sodium channel