title: Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell.
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-beta (ERbeta). 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.
authors.affiliation: Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sasahara
authors.forename: Hanako
authors.initials: H
authors.lastname: Shikimi
authors.forename: Shogo
authors.initials: S
authors.lastname: Haraguchi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Honda
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Harada
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000172:deficiency; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol; D001141:Aromatase