SAT-708 The Effect of Soybean Isoflavones in Developing Cerebellum

Abstract ENDO 2020 The effect of soybean isoflavones in developing cerebellum Thyroid hormone (TH) receptor (TR) and estrogen receptor (ER) play crucial roles in cerebellar development. TR and ER are involved in Purkinje cells dendrite growth, spines and synapse formation. They also regulate the functional maturation, intracellular metabolism, and migration of neuron and glial. Soybean isoflavones especially genistein, daidzein, and daidzein metabolite, S-equol were known to exert their action through TR, ER, and GPR30, that is a G-protein-coupled ER. However, the mechanisms of soybean isoflavone action on cerebellar development and function have not yet been extensively studied. We evaluated the effects of soybean isoflavone, such as genistein, daidzein, and S-equol, using mouse primary cerebellar culture, astrocyte-enriched culture, and C6 clonal cells. Soybean isoflavone augmented TH- or estradiol (E2)-mediated dendrite arborization of Purkinje cells. Such augmentation was suppressed by G15, a selective G-protein coupled ER (GPR30) antagonist, and ICI 182.780, an antagonist for ERs in both cultures. It also increased mRNA expression level of TH-responsive genes including Mbp, Bdnf, Rc3, Ntf3, Camk2b, and Hr. Moreover, genistein and daidazein also increased mRNA expression level of Syn1, Syp and Psd95 that are involved in synaptic plasticity. On the other hand, in astrocytes, soybean isoflavone activated cell migration and F-actin rearrangements. Such effects were suppressed by G15, but not by ICI 182.780. Knockdown of GPR30 by RNAi also suppressed the cells migration. Protein expression levels of p-Akt (Ser473), p-Rac1/cdc42 (Ser71), RhoA, Rac1/2/3, and cdc42 also increased by soybean isoflavone. Co-exposure with Rhosin HCl, a selective RhoA inhibitor, reduced the cells migration and formation of stress fibers. These findings indicate that sobybean isoflavone may affect cerebellar development by acting to both neurons and astrocytes through several signaling pathways, including TR, ER, and GPR30. Keywords: EDC, ER, TR, GPR30, Neuron, Astrocyte