title: Estrogen enhances depolarization-induced glutamate release through activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase in cultured hippocampal neurons.
abstract: Changes in synaptic efficacy are considered necessary for learning and memory. Recently, it has been suggested that estrogen controls synaptic function in the central nervous system. However, it is unclear how estrogen regulates synaptic function in central nervous system neurons. We found that estrogen potentiated presynaptic function in cultured hippocampal neurons. Chronic treatment with estradiol (1 or 10 nm) for 24 h significantly increased a high potassium-induced glutamate release. The estrogen-potentiated glutamate release required the activation of both phosphatidylinositol 3-kinase and MAPK. The high potassium-evoked release with or without estradiol pretreatment was blocked by tetanus neurotoxin, which is an inhibitor of exocytosis. In addition, the reduction in intensity of FM1-43 fluorescence, which labeled presynaptic vesicles, was enhanced by estradiol, suggesting that estradiol potentiated the exocytotic mechanism. Furthermore, protein levels of synaptophysin, syntaxin, and synaptotagmin (synaptic proteins, respectively) were up-regulated by estradiol. We confirmed that the up-regulation of synaptophysin was blocked by the MAPK pathway inhibitor, U0126. These results suggested that estrogen enhanced presynaptic function through the up-regulated exocytotic system. In this study, we propose that estrogen reinforced excitatory synaptic transmission via potentiated-glutamate release from presynaptic sites.
authors.affiliation: Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yokomaku
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Numakawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.forename: Chika
authors.initials: C
authors.lastname: Nishio
authors.forename: Takahisa
authors.initials: T
authors.lastname: Taguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatanaka
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011374:Progesterone / Q000494:pharmacology; D050765:Qa-SNARE Proteins; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D016708:Synaptophysin / Q000187:drug effects / Q000378:metabolism; D050857:Synaptotagmins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D018698:Glutamic Acid; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011374:Progesterone; D050765:Qa-SNARE Proteins; D016708:Synaptophysin; D050857:Synaptotagmins; D005680:gamma-Aminobutyric Acid