Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus

Abstract

Background: Pyrethroids have been widely used in residential and agricultural areas. However, little is known about the effects of prenatal exposure to deltamethrin on cognition in early development of offspring. In this study, the effects of prenatal exposure to deltamethrin on learning and memory abilities, N-methyl-D-aspartate receptor (NMDAR) subunits, brain derived neurotrophic factor (BDNF), Tyrosine kinase B (TrkB) receptor, and phosphorylated cAMP response element binding protein (pCREB) in the hippocampus of offspring rats were investigated.Experimental Approaches: Groups each of six female SD rats, as F0-generation, were administered with deltamethrin (0, 0.54, 1.35, and 2.7, 9 mg/kg), or memantine (10 mg/kg), or co-administered with deltamethrin (9 mg/kg) and memantine (10 mg/kg) daily by gavage during pregnancy. The learning and memory ability was evaluated using Morris water maze (MWM) task on postnatal day 21. The expression of NMDAR (GluN1, GluN2A, and GluN2B), BDNF, pTrkB/TrkB, and pCREB/CREB in hippocampus were assessed with western blotting.Results: Prenatal exposure to a relatively low dose of deltamethrin (2.7, 1.35, and 0.54 mg/kg) had no impact on learning and memory abilities or the expression of NMDAR, BDNF, pTrkB, and pCREB in the hippocampus of the exposed offspring. The group treated with 9 mg/kg deltamethrin showed impaired cognitive abilities and decreased expression levels of GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB in the hippocampus. However, the declined cognitive ability were ameliorated by memantine treatment with increased GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB expression in the hippocampus.Conclusion and Implications: Prenatal exposure to a relatively high does of deltamethrin (9 mg/kg) alters cognition in offsprings and that this cognitive dysfunction can be ameliorated by memantine treatment. Moreover, NMDAR/BDNF signaling may be associated with the effects of prenatal exposure to deltamethrin on cognitive ability in offspring.

Developmental pyrethroid exposure and age influence phenotypes in a Chd8 haploinsufficient autism mouse model

“…Developmental DM exposure in rodents has also been associated with increased impulsivity and reduced attention 25 , deficits in working memory in a Y-maze 25 , 48 , and impaired learning and memory in the Morris water maze task 47 , 49 . Anxiety-like behavior has also been reported in acutely exposed adult rats showing reduced arm entries, reduced time in open arms, and fewer center crossings in the elevated plus maze 50 .…”

Repetitive transcranial magnetic stimulation promotes neural functional recovery via upregulation of synaptic plasticity-related proteins in rats with traumatic brain injury

“…NMDA receptors are an important mediator of brain plasticity and can transform speci c neuronal activity patterns into changes in synaptic structure and function [30], which is considered the basis of changes in behavioral function. NMDAR1 is present in all endogenous NMDARs and is widely expressed throughout development [31,32]. Activation of NMDAR1 in the hippocampus CA1 area is known to play an important role in LTP induction related to learning and memory ability [33][34][35].…”

Deltamethrin Exposure Inhibits Adult Hippocampal Neurogenesis and Causes Deficits in Learning and Memory in Mice

“…Recently, occupational exposure to pyrethroids during adulthood have been associated with increased risk of Parkinson disease (Furlong et al, 2015) and developmental exposures have been linked to increased risk of developing autism spectrum disorders (Shelton et al, 2014) and attention deficit hyperactivity disorder (Richardson et al, 2015;Wagner-Schuman et al, 2015). Furthermore, developmental exposure to deltamethrin has been shown to cause memory deficits in water maze, conditioned fear, and/or object recognition (Pitzer et al, 2019;Zhang et al, 2018). Deltamethrin is one of the most commonly used type II pyrethroid insecticides in home and agriculture and is also found as an ingredient in flea and tick repellents and are available at sporting goods stores for treating fabrics (Furlong et al, 2017;Md Meftaul et al, 2020).…”