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PMID: 10725383 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 7 ·2000-03-28 ·Pages 3602-7

Bi R, Broutman G, Foy MR, Thompson RF, Baudry M

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.

MeSH Terms
Action Potentials Alzheimer Disease/drug therapy Animals Estrogens/pharmacology,therapeutic use Hippocampus/drug effects,enzymology,metabolism,physiology In Vitro Techniques MAP Kinase Signaling System Phosphorylation Protein-Tyrosine Kinases/metabolism Rats Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors,metabolism
Chemicals
Estrogens Receptors, N-Methyl-D-Aspartate Protein-Tyrosine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bi R
Neuroscience Program, University of Southern California, Los Angeles, CA 90089-2520, USA.
Broutman G
Foy M R
Thompson R F
Baudry M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.060034497
Published
2000-03-28
Pages
3602-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16286
Subset
IM
Grants
NIA NIH HHS · P01 AG014751 · United States
NIA NIH HHS · AG-14751 · United States
External Links
PubMed source DOI: 10.1073/pnas.060034497 PMC Full Text View journal details
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