Interaction between cell membrane and nuclear hormone receptor in brain development and its modification by environmental chemicals

去年，我试图完成我的研究项目，在环境化学品和甲状腺激素（TH）与核受体（甲状腺激素受体和雌激素受体）或细胞表面受体（整合素和GPER 1/GPR 30）的相互作用，调节细胞增殖，迁移，神经突生成和突触发生。结果表明，甲状腺激素通过TRα依赖性和TR非依赖性途径诱导细胞迁移和增殖。甲状腺激素诱导的细胞迁移和增殖通过激活Grb 2导致激活TR非依赖性途径。此外，环境化学物质如胆甾酮或钆基造影剂（GBCA）通过GPER 1或整合素激活加速细胞迁移，这导致激活FAK/PI 3 K/Akt/Rho-GT3途径，诱导F-肌动蛋白重排。TH和β-羟色胺酮还分别通过TRα和ERα两条不同的机制途径诱导浦肯野细胞的树突和突触发生。细胞分级分离实验表明，多巴胺能神经元诱导SNARE蛋白定位于细胞膜和树突部分，提示突触形成。异黄酮和TH也增加了突触前和突触后蛋白的表达水平。现在，我正在准备几篇论文来发表我的研究成果。我们计划在几个国际期刊上发表我们的研究结果。

Last year, I have tried to finish my research project in the interaction of environmental chemicals and thyroid hormones (TH) with the nuclear receptor (thyroid hormone receptor and estrogen receptor) or cell surface receptor (integrin and GPER1/GPR30) that regulate cell proliferation, migration, neuritogenesis, and synaptogenesis. The results revealed that thyroid hormones induced cell migration and proliferation through TRα-dependent and TR-independent pathways. The thyroid hormone-induced cell migration and proliferation through the activation of Grb2 leads to activate the TR-independent pathways. In addition, environmental chemicals such as isoflavones or gadolinium-based contrast agents (GBCAs) accelerate cell migration through GPER1 or integrin activation, which leads to activate FAK/PI3K/Akt/Rho-GTPase pathways that induced F-actin re-arrangement. TH and isoflavones also induced dendritogenesis and synaptogenesis in Purkinje cells via different mechanism pathways, TRα and ERα, respectively. Cell fractionation assays showed that isoflavones induced localization of SNARE protein to the membrane and dendritic fraction, indicate the synapse formation. Isoflavones and TH also increased the expression level of both pre- and post-synaptic proteins. Now, I am preparing several manuscripts to publish my research results. We plan to publish our results in several international journals.