Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell

Katsunori Sasahara, Hanako Shikimi, Shogo Haraguchi, Hirotaka Sakamoto, Shin Ichiro Honda, Nobuhiro Harada, Kazuyoshi Tsutsui

    Research output: Contribution to journalArticle

    98 Citations (Scopus)

    Abstract

    Neurosteroids are synthesized de novo from cholesterol in the brain. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently, we identified the Purkinje cell as an active neurosteroidogenic cell. In rodents, this neuron actively produces several 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 neuronal synaptic contact, because the Purkinje cell expresses estrogen receptor-β(ERβ). To test this hypothesis, in this study we examined the effects 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. To elucidate the mode of action of estradiol, we further examined the expression of brain-derived neurotrophic factor (BDNF) in response to estrogen actions in the neonate. Estrogen administration to neonatal WT or ArKO mice increased the BDNF level 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.

    Original languageEnglish
    Pages (from-to)7408-7417
    Number of pages10
    JournalJournal of Neuroscience
    Volume27
    Issue number28
    DOIs
    Publication statusPublished - 2007 Jul 11

    Keywords

    • Brain-derived neurotrophic factor
    • Cerebellar neuronal circuit formation
    • Cytochrome P450 aromatase
    • Dendritic outgrowth
    • Development
    • Estradiol
    • Knock-out mice
    • Neurosteroids
    • Purkinje cell
    • Spine formation
    • Synapse formation

    ASJC Scopus subject areas

    • Neuroscience(all)

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