Estradiol Promotes Purkinje Dendritic Growth, Spinogenesis, and Synaptogenesis During Neonatal Life by Inducing the Expression of BDNF

Shogo Haraguchi, Katsunori Sasahara, Hanako Shikimi, Shin-ichiro Honda, Nobuhiro Harada, Kazuyoshi Tsutsui

Neurosteroids are synthesized de novo from cholesterol in the brain. In rodents, the Purkinje cell actively produces several kinds of neurosteroids including estradiol during neonatal life, when cerebellar neuronal circuit formation occurs. Estradiol may be involved in cerebellar neuronal circuit formation through promoting neuronal growth and synaptic contact, because the Purkinje cell expresses estrogen receptor-β. To test this hypothesis, in this study we examined the effect of estradiol on dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell using neonatal wild-type (WT) mice or cytochrome P450 aromatase knock-out (ArKO) mice. Administration of estradiol to neonatal WT or ArKO mice increased dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell. In contrast, WT mice treated with tamoxifen, an ER antagonist, or ArKO mice exhibited decreased Purkinje dendritic growth, spinogenesis, and synaptogenesis at the same neonatal period. Estrogen administration to neonatal WT or ArKO mice increased the expression of brain-derived neurotrophic factor (BDNF) in the cerebellum, whereas tamoxifen decreased the BDNF level in WT mice similar to ArKO mice. BDNF administration to tamoxifen-treated WT mice increased Purkinje dendritic growth. These results indicate that estradiol induces dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell via BDNF action during neonatal life.