Early‐life exposure to low levels of permethrin exerts impairments in learning and memory with the effects on neuronal and glial population in adult male mice

Abstract

Permethrin, a pyrethroid chemical, is widely used as a pesticide because of its rapid insecticidal activity. Although permethrin is considered to exert very low toxicity in mammals, the effects of early, low‐level, chronic exposure on the adult central nervous system are unclear. In this study, we investigated the effects of low‐level, chronic permethrin exposure in early life on the brain functions of adult mice, using environmentally relevant concentrations. We exposed mice to the acceptable daily intake level of permethrin (0.3 ppm) in drinking water during the prenatal and postnatal periods. We then examined the effects on the central nervous system in adult male offspring. In the permethrin group, we detected behavior that displayed incomplete adaptation to a novel environment, as well as an impairment in learning and memory. In addition, immunohistochemical analysis revealed an increase in doublecortin‐ (an immature neuron marker) positive cells in the hippocampal dentate gyrus in the permethrin exposure group compared with the control group. Additionally, in the permethrin exposure group there was a decrease in astrocyte number in the hilus of the dentate gyrus, and remaining astrocytes were often irregularly shaped. These results suggest that exposure to permethrin at low levels in early life affects the formation of the neural circuit base and behavior after maturation. Therefore, in the central nervous system of male mice, low‐level, chronic permethrin exposure during the prenatal and postnatal periods has effects that were not expected based on the known effects of permethrin exposure in mature animals.

Varying modalities of perinatal exposure to a pesticide cocktail elicit neurological adaptations in mice and zebrafish

“…For instance, mice perinatally exposed to elevated concentrations of malathion developed anxiety-like traits and presented with impairment of social interactions (Ouardi et al, 2019). Perinatal exposure to the insecticide permethrin was associated with an incomplete adaptation to a novel environment, as well as an impairment in learning and memory in adult males (Saito et al, 2019). Exposure to high concentrations of glyphosate during gestation and lactation, delayed innate reflexes and caused a deficit in motor development (Ait-Bali et al, 2020), as well as autism spectrum disorder-like behaviors (Pu et al, 2020).…”

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…Permethrin mainly affects the central nervous system and causes progressive aggregation of α-synuclein, loss of dopaminergic neurons, and muscle spasms [ 240 , 241 ]. Permethrin doses from two publications that were published last five years showed 0.05–34 mg/kg/day by oral administration [ 205 , 206 ]. Early-life exposure to permethrin as progressive PD animal models produces PD symptoms such as loss of striatal dopaminergic neurons, mitochondrial dysfunction, and motor impairments in adult life stages.…”

“…Early-life exposure to permethrin as progressive PD animal models produces PD symptoms such as loss of striatal dopaminergic neurons, mitochondrial dysfunction, and motor impairments in adult life stages. The behavioral tests applied in this type of PD model are rotarod, footprint, beam walk, light/dark transition, and fear conditioning tests [ 205 , 206 ].…”

“…Saito et al (2019) exposed C57BL/6 mice to permethrin (0.3 ppm) in drinking water all through the prenatal and postnatal periods and studied the effects on the central nervous system in adult male mice [ 205 ]. They applied open-field test, light/dark transition test, and contextual/cued fear conditioning test for behavioral analysis and found that early life exposure to low levels of permethrin caused motor, learning, and memory impairments in mice [ 205 ]. Nasuti et al (2017) administered permethrin at the dose of 34 mg/kg daily from the postnatal 6th–21st days and evaluated the effect of early exposure of permethrin-induced PD in Wistar rats.…”

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

“…Pesticide exposure has been extensively linked to developmental defects [141], and is known to affect neural stem cells and neural progenitor cells in the pre-and postnatal periods [142,143]. While early life exposure to pesticides affect both neurons and glia, and impairs learning and memory [144], pesticides could also potentially impact on the arguably more AD-relevant process of adult neurogenesis, particularly at the hippocampal neurogenic sites [145]. Adult neurogenesis at the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus (DG) in the hippocampus has been demonstrated extensively in rodent animal models, and is functionally linked to memory encoding as well as behavioral modification [145,146].…”