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

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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 - Jul 11 2007
Externally publishedYes

Fingerprint

Purkinje Cells
Aromatase
Brain-Derived Neurotrophic Factor
Estradiol
Estrogens
Knockout Mice
Neurotransmitter Agents
Tamoxifen
Growth
Brain
Estrogen Receptors
Cytochrome P-450 Enzyme System
Cerebellum
Rodentia
Cholesterol
Neurons

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)

Cite this

Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell. / Sasahara, Katsunori; Shikimi, Hanako; Haraguchi, Shogo; Sakamoto, Hirotaka; Honda, Shin Ichiro; Harada, Nobuhiro; Tsutsui, Kazuyoshi.

In: Journal of Neuroscience, Vol. 27, No. 28, 11.07.2007, p. 7408-7417.

Research output: Contribution to journalArticle

Sasahara, Katsunori ; Shikimi, Hanako ; Haraguchi, Shogo ; Sakamoto, Hirotaka ; Honda, Shin Ichiro ; Harada, Nobuhiro ; Tsutsui, Kazuyoshi. / Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 28. pp. 7408-7417.
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AU - Sasahara, Katsunori

AU - Shikimi, Hanako

AU - Haraguchi, Shogo

AU - Sakamoto, Hirotaka

AU - Honda, Shin Ichiro

AU - Harada, Nobuhiro

AU - Tsutsui, Kazuyoshi

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KW - Spine formation

KW - Synapse formation

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