S-equol is a major bacterial metabolite of the soy isoflavone daidzein. It is known
to be a phytoestrogen that acts by binding to the nuclear estrogen receptors (ERs)
that are expressed in various brain regions, including the cerebellum. However, the
effects of S-equol on cerebellar development and function have not yet been extensively
studied. In this study, the effects of S-equol were evaluated using a mouse primary
cerebellar culture, Neuro-2A clonal cells, and an astrocyte-enriched culture. S-equol
augmented the dendrite arborization of Purkinje cells induced by triiodothyronine
(T-3) and the neurite growth of Neuro-2A cell differentiation. 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. On the other hand, in astrocytes, S-equol
induced cell proliferation and cell migration with an increase in the phosphorylated
extracellular-signal-regulated kinase 1/2 and F-actin rearrangements. Such effects
were suppressed by G15, but not by ICI. These findings indicated that S-equol may
enhanced cerebellar development by affecting both neurons and astrocytes through several
signaling pathways, including GPR30 and ERs. We here report a novel mechanism of S-equol
in cerebellar development that may provide a novel possibility to use S-equol supplementation
during development.
