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Isoflavones Mediate Dendritogenesis Mainly through Estrogen Receptor α
Winda Ariyani1,2, Izuki Amano2, Noriyuki Koibuchi2
1Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi 371-8512, Japan.
International Journal of Molecular Sciences
|May 27, 2023
Summary
Soybean isoflavones promote brain cell growth by activating estrogen receptors (ERs) and G-protein-coupled ER (GPER1). ERα is key for neuron development, while GPER1 supports astrocyte communication, both crucial for brain plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Endocrinology
Background:
- Nuclear estrogen receptor (ER) and G-protein-coupled ER (GPER1) are vital for brain development, influencing dendrite growth and synapse formation.
- Soybean isoflavones like genistein, daidzein, and S-equol act via ER and GPER1, but their precise roles in dendritogenesis and neuritogenesis are not fully understood.
Purpose of the Study:
- To investigate the mechanisms by which soybean isoflavones influence neuronal development, specifically dendrite and neurite outgrowth.
- To elucidate the roles of ERα, ERβ, and GPER1 in mediating these isoflavone effects in neuronal and astrocyte cultures.
Main Methods:
- Primary mouse cerebellar and astrocyte-enriched cultures, Neuro-2A cells, and neuron-astrocyte co-cultures were used.
- Effects of isoflavones on dendrite arborization and neurite outgrowth were assessed, along with the impact of ER/GPER1 antagonists (ICI 182,780, G15) and gene knockdown.
- Changes in mRNA levels of ER-responsive genes and receptor protein levels were analyzed.
Main Results:
- Soybean isoflavones augmented estradiol-mediated dendrite arborization in Purkinje cells, an effect blocked by ER/GPER1 antagonists and gene knockdown.
- ERα knockdown most significantly reduced isoflavone-induced neurite outgrowth and the expression of key neuronal genes (Bdnf, Camk2b, Rbfox3, Tubb3, Syn1, Dlg4, Syp).
- Isoflavones increased ERα levels and promoted astrocyte proliferation via ER and GPER1, highlighting astrocyte involvement in isoflavone-driven neurogenesis.
Conclusions:
- Estrogen receptor alpha (ERα) plays a critical role in soybean isoflavone-induced neuritogenesis.
- GPER1 signaling is essential for astrocyte proliferation and astrocyte-neuron communication, contributing to the overall neurodevelopmental effects of isoflavones.
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