LCT Disrupts The Promotion Of E₂ On PSD95 Expression In Hippocampus Via BDNF Pathway

Background:Lambda-cyhalothrin is a kind of widely used II type of pesticides which has neurotoxicity. Recent study found that to adolescence ovariectomized mice, LCT or estrogen can improve the protein expression of PSD95 and improve the ability of learning and memory. When combination use of E2 and LCT, there does not show their individual effects. In primary hippocampal neuron culture model, LCT disrupts the up-regulation effect of 17β-estradiol on PSD 95 Protein expression and neurite growth(performance increase for the number) via ERα-dependent Akt pathway signaling. BDNF can regulate neuronal survival and growth and synaptic development, which is an important effector molecule to E2 neuroprotection. The expression of BDNF could be regulated by ERα-AKT,MAPK and PKA several signaling pathways. Although LCT can disturb ERα-AKT pathway, not necessarily influence BDNF. This topic is aimed at the problem of research.Objective:The mouse hippocampal cell line HT22 cells were used to be an in vitro model, and the female ICR mice ovarian resection animal model in vivo.To explore the effect of BDNF pathway on LCT influencing estrogen promoting the expression of PSD95 in hippocampus neurons and promoting hippocampal function.Methods :HT22 cells were treated with LCT(50 μM), E2(10 n M),LCT(50 μM)+Trk B FC(20 μg/ml), E2(10 n M)+Trk B FC(20 μg/ml),LCT(50 μM)+ICI182 780(1 μM), E2(10 n M)+ ICI182 780(1 μM),LCT(50 μM)+ E2(10 n M)for 24 h. MTT kit was used to detect cell viability. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor(BDNF) of culture supernatant and cell. PND28 of female mice were received ovariectomy. After 7 days for recovery, mice were treated with OVX+DMSO,OVX+LCT(3.0 μg/g),OVX+ E2(10.0 μg/g),LCT(3.0 μg/g)+K252a(25 μg/kg),E2(10.0 μg/g)+K252a(25 μg/kg),LCT(3.0 μg/g)+ E2(10.0 μg/g), Sham+DMSO, Sham+LCT(3.0 μg/g) for 7 days. The researchs(Morris water maze and open field test) were initiated 24 h later. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor(BDNF).Results:In HT22 cells, LCT or E2 could promote the expression of PSD95 and BDNF,blocked by Trk B FC. However,the promotion of PSD95 and BDNF were inhibited when combination use of E2 and LCT. In OVX mice, the expression of PSD95 and BDNF were declined when mice were treated with OVX. The effects were reversed when supplying with E2, the expression of PSD95 and BDNF declined in OVX+ E2 compared to OVX+DMSO; LCT may suppress the up-regulation effect of E2 on PSD95 and BDNF in OVX mice. The expression of PSD95 and BDNF were incerased in OVX+LCT compared to OVX+DMSO; However, LCT or E2 alone could increase the expression of PSD95 and BDNF protein in the hippocampus of mice, while K252 a could block the effect; The promotion of PSD95 and BDNF were inhibited when combination use of E2 and LCT. The expression of PSD95 and BDNF were incerased in OVX+LCT+ E2 compared to OVX+ E2. At the same time in the behavioral experiments also found similar to the effect, LCT or E2 alone treatment can increase the exploration ability and the ability of learning and memory in mice, while K252 a can block the effect. When LCT and E2 are acting together, their respective effects disappear.Conclusions :BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells. Although LCT alone has a similar effect on E2. LCT could disrupt the promotion of E2 on PSD95 expression and hippocampal function via BDNF pathway.