Early postnatal exposure to permethrin and deltamethrin mixtures induces sex-specific hippocampal neurobehavioral and neurochemical alterations in adulthood.

Pyrethroid insecticides, including deltamethrin and permethrin, are known for their individual toxic effects; however, evidence regarding their combined toxicity during early developmental stages remains limited. The present study aimed to investigate the neurotoxic effects of co-exposure to deltamethrin and permethrin in lactating rats, focusing on emotional and cognitive behaviors, as well as cholinergic and monoaminergic neurotransmission in their progeny at adulthood (5 months of age). Dams were orally administered deltamethrin (1.35 mg/kg/day) and permethrin (34 mg/kg/day), either individually or in combination, from postnatal day (PND) 7 to PND 21. Our results demonstrated that co-exposure of lactating females to deltamethrin and permethrin induced behavioral alterations in their offspring, including impaired locomotor activity, anxiety-like behavior, and learning and memory deficits, with sex-specific effects. Furthermore, these toxicants triggered oxidative stress in the hippocampus, as indicated by elevated levels of malondialdehyde, nitric oxide, and advanced oxidation protein products, along with impaired enzymatic and non-enzymatic antioxidant defenses. Early postnatal exposure also caused sex-dependent modifications in monoamine concentrations across multiple brain regions. Mechanistically, molecular alterations of the cholinergic system were observed in the hippocampus of both male and female rats, as evidenced by downregulation of AChE, mAChR, and nAChR gene expression. These molecular changes were further confirmed by histological analyses. In conclusion, our findings demonstrate that exposure of lactating females to deltamethrin and permethrin, individually or in combination, induces sex-dependent, deleterious, and sometimes distinct neurodevelopmental effects in their offspring at PND 150.