Developmental pyrethroid exposure causes long-term decreases of neuronal sodium channel expression.

Developmental pyrethroid exposure causes long-term decreases of neuronal sodium channel expression.

Magby Jason P; Richardson Jason R

Neurotoxicology

2017

2017-05

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 Nav mRNA expression. However, it is unknown whether this occurs in vivo. To determine whether developmental pyrethroid exposure decreases Nav mRNA expression, pregnant mice were exposed to the pyrethroid deltamethrin (0 or 3mg/kg) every three days throughout gestation and lactation. Nav mRNA 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 Nav mRNA 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 Nav and BDNF mRNA expression that may contribute to long-term behavioral deficits.

Animals; BDNF; Brain-Derived Neurotrophic Factor/metabolism; Cerebral Cortex/*drug effects/growth & development/metabolism; Corpus Striatum/*drug effects/growth & development/metabolism; Deltamethrin; Female; Inbred C57BL; Insecticides/*toxicity; Male; Messenger/metabolism; Mice; Neurodevelopmental; Neurons/*drug effects/metabolism; Nitriles/*toxicity; Pregnancy; Prenatal Exposure Delayed Effects/*metabolism; Pyrethrins/*toxicity; Pyrethroid; RNA; Sodium channel; Voltage-Gated Sodium Channels/*metabolism

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