Influence of bifenthrin exposure at different gestational stages on the neural development

Perinatal exposure to bifenthrin (BF) alters neurodevelopment. However, the most susceptible time period to BF exposure and the possible mechanisms are not clear. In the current study, pregnant female mice were treated with BF (0.5 mg/kg/d) at three different stages [gestational day (GD) 0-5, 6-15 and 16-birth (B)] and neurologic deficits were evaluated in offspring mice. BF exposure at GD 16-B significantly altered the locomotor activity and caused learning and memory impairments in 6-week-old offspring. Gestational BF exposure also caused neuronal loss in the region of cornu ammonis of hippocampi of 6-week-old offspring. Interestingly, neurobehavioral impairments and neuronal loss were not observed in offspring at 10-week-old. BF exposure at GD 16-B also decreased protein levels of VGluT1, NR1 and NR2A while increased the protein levels of NR2B and VGAT1, as well as the gene levels of Il-1β, Il-6 and Tnf-α in hippocampi of 6-week-old offspring. Collectively, these data demonstrate that gestational exposure to a low dose BF causes neurodevelopmental deficits that remit with the age and the late-stage of pregnancy is the most susceptible time window to BF exposure. Imbalance in excitatory/inhibitory neuronal transmission, altered expression levels of NMDA receptors and increased neural inflammation may be associated with BF prenatal exposure-triggered neurobehavioral impairments.