Lambda-cyhalothrin Disrupts The Up-regulation Effect Of 17β-estradiol On Post-synaptic Density 95 Protein Expression Via Estrogen Receptor α-dependent Akt Pathway

BackgroundLambda-cyhalothrin(LCT) is one of the type Ⅱ pyrethroid insecticide which has been widely used in agriculture, forestry and public health because of the broad spectrum and the better insecticidal activity. The main effect of LCT is to disrupt the voltage-gated sodium channels, causing the depolarization of nerve membrane and influencing the action potential. Recent studies demonstrated early postnatal exposure to LCT could induce the impairs in learning and memory in mice, however, there was a gender difference in postsynaptic density protein 95(PSD95) expression. The PSD95, which is involved in the development of the structure and function of the new spines and localized with estrogen receptor α(ERα) at the post-synaptic density, could be regulated by estrogen(E2) through PI3K-Akt signaling. Recent studies have illustrated LCT could disrupt the development of reproductive system with its endocrine disrupting action(estrogenic effect). However, whether LCT will induce developmental neurotoxicity via disrupting E2 effect is not clear.ObjectiveTo explore whether LCT will influence the effect of 17β-estradiol on PSD95 expression through the estrogenic effect.MethodsThe primary hippocampal neuron culture model and HT22 cell line were used to investigate the LCT toxicology of neurodevelopment. Cells were cultured for 7 days,and then were treated with DMSO, E2(10 n M), LCT(50 μM), E2(10 n M)+ICI182,780(1 μM), E2(10 n M)+LY294,002(1 μM), LCT(50 μM)+ICI182,780(1 μM), LCT(50 μM)+LY294,002(1 μM), E2(10 n M)+ LCT(50 μM) for 24 hrs. CCK-8 kit was used to detect the cell viability. The neurite outgrowth was detected by immunocytochemistry, estrogen receptor α(ERα) and PSD95 expression were measured by western blot. The m RNA of PSD95 was measured by q PCR.ResultsIn primary hippocampal neuron culture model, treatment of LCT or E2 could promote neurite outgrowth and fluorescence intensity of PSD95(P<0.05). However, when combination use of E2 and LCT, the neurite outgrowth and PSD95 expression were inhibited compared to E2 or LCT treatment. In HT22 cells, treatment of LCT or E2 could increase PSD95 and ERα protein expression with the higher levels of phosphorylation of Akt and 4E-BP1(P<0.05). The PSD95 m RNA and phosphorylation of CREB had no changes. When combination use of E2 and LCT, there were no changes in PSD95 and ERα protein, and the phosphorylation of Akt and 4E-BP1 were also inhibited compared to E2 or LCT treatment(P<0.05). All these promotion of E2 or LCT could be blocked by ICI182,780 and LY294,002(P<0.05).ConclusionsLCT disrupts the up-regulation effect of 17β-estradiol on PSD 95 Protein expression via ERα-dependent Akt pathway signaling.