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，即环境化学物质和甲状腺激素(TH)与调节细胞增殖、迁移、神经发生和突触发生的核受体(甲状腺激素受体和雌激素受体)或细胞表面受体(整合素和GPER1/GPR30)的相互作用。结果表明，甲状腺激素通过α依赖性和非依赖性途径诱导细胞迁移和增殖。甲状腺激素通过激活Grb2诱导细胞迁移和增殖，从而激活不依赖于tr的途径。此外，环境化学物质如异黄酮类或基于Gd的造影剂(GBCA)通过激活GPER1或整合素来加速细胞迁移，从而激活FAK/PI3K/Akt/Rho-GTPase通路，从而诱导F-肌动蛋白重排。TH和异黄酮类化合物还通过不同的机制分别诱导浦肯野细胞树突状突起和突触发生，分别是TRα和ERα。细胞分级分析表明，异黄酮诱导SNARE蛋白定位于膜和树突状部分，表明突触的形成。异黄酮类和TH也增加了突触前和突触后蛋白的表达水平。现在，我正在准备几份稿件，以发表我的研究成果。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.