title: The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus.
abstract: Estrogen replacement therapy in women is associated with improvement of cognitive deficits and reduced incidence of Alzheimer's disease. The present study indicates that estrogen is neuroprotective against N-methyl-d-aspartate (NMDA)- and kainate-mediated neurotoxicity, an effect mediated by tyrosine kinase/mitogen-activated protein kinase (MAPK) pathways. Estrogen also stimulates tyrosine phosphorylation of NMDA receptors via an src tyrosine kinase/MAPK pathway. Finally, estrogen-mediated enhancement of long-term potentiation in hippocampal slices is mediated by activation of an src tyrosine kinase pathway. Thus, estrogen, by activating an src tyrosine kinase and the extracellular signal-related protein kinase/MAPK signaling pathway, both enhances NMDA receptor function and long-term potentiation and retains neuroprotective properties against excitotoxicity. These findings warrant further evaluation of the usefulness of estrogenic compounds for the treatment of Alzheimer's disease and other neurodegenerative diseases.
authors.affiliation: Neuroscience Program, University of Southern California, Los Angeles, CA 90089-2520, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bi
authors.forename: G
authors.initials: G
authors.lastname: Broutman
authors.forename: M R
authors.initials: MR
authors.lastname: Foy
authors.forename: R F
authors.initials: RF
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: Baudry
mesh_terms: D000200:Action Potentials; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004967:Estrogens; D016194:Receptors, N-Methyl-D-Aspartate; D011505:Protein-Tyrosine Kinases