PMID- 17626201 OWN - NLM STAT- MEDLINE DCOM- 20070807 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 27 IP - 28 DP - 2007 Jul 11 TI - Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell. PG - 7408-17 AB - 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. FAU - Sasahara, Katsunori AU - Sasahara K AD - Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan. FAU - Shikimi, Hanako AU - Shikimi H FAU - Haraguchi, Shogo AU - Haraguchi S FAU - Sakamoto, Hirotaka AU - Sakamoto H FAU - Honda, Shin-ichiro AU - Honda S FAU - Harada, Nobuhiro AU - Harada N FAU - Tsutsui, Kazuyoshi AU - Tsutsui K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Estrogen Antagonists) RN - 0 (Estrogens) RN - 094ZI81Y45 (Tamoxifen) RN - 4TI98Z838E (Estradiol) RN - EC 1.14.14.1 (Aromatase) SB - IM MH - Aging/physiology MH - Animals MH - Animals, Newborn MH - Aromatase/deficiency MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/metabolism/physiology MH - Cerebellum/drug effects/metabolism MH - Dendrites/drug effects/*physiology MH - Dendritic Spines/drug effects/*physiology MH - Estradiol/pharmacology MH - Estrogen Antagonists/pharmacology MH - Estrogens/*biosynthesis MH - Female MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Purkinje Cells/metabolism/*physiology MH - Synapses/drug effects/*physiology MH - Tamoxifen/pharmacology PMC - PMC6672615 EDAT- 2007/07/13 09:00 MHDA- 2007/08/08 09:00 PMCR- 2008/01/11 CRDT- 2007/07/13 09:00 PHST- 2007/07/13 09:00 [pubmed] PHST- 2007/08/08 09:00 [medline] PHST- 2007/07/13 09:00 [entrez] PHST- 2008/01/11 00:00 [pmc-release] AID - 27/28/7408 [pii] AID - 3243346 [pii] AID - 10.1523/JNEUROSCI.0710-07.2007 [doi] PST - ppublish SO - J Neurosci. 2007 Jul 11;27(28):7408-17. doi: 10.1523/JNEUROSCI.0710-07.2007.