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PMID: 17379265 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications.

Steroids ·Vol. 72 ·No. 5 ·2007-05-00 ·Pages 381-405

Brann DW, Dhandapani K, Wakade C, Mahesh VB, Khan MM

Abstract

Estrogen is an important hormone signal that regulates multiple tissues and functions in the body. This review focuses on the neurotrophic and neuroprotective actions of estrogen in the brain, with particular emphasis on estrogen actions in the hippocampus, cerebral cortex and striatum. Sex differences in the risk, onset and severity of neurodegenerative disease such as Alzheimer's disease, Parkinson's disease and stroke are well known, and the potential role of estrogen as a neuroprotective factor is discussed in this context. The review assimilates a complex literature that spans research in humans, non-human primates and rodent animal models and attempts to contrast and compare the findings across species where possible. Current controversies regarding the Women's Health Initiative (WHI) study, its ramifications, concerns and the new studies needed to address these concerns are also addressed. Signaling mechanisms underlying estrogen-induced neuroprotection and synaptic plasticity are reviewed, including the important concepts of genomic versus nongenomic mechanisms, types of estrogen receptor involved and their subcellular targeting, and implicated downstream signaling pathways and mediators. Finally, a multicellular mode of estrogen action in the regulation of neuronal survival and neurotrophism is discussed, as are potential future directions for the field.

MeSH Terms
Animals Cell Survival/drug effects Disease Models, Animal Estrogens/metabolism,therapeutic use Genome, Human/drug effects Humans Neurodegenerative Diseases/drug therapy,genetics,metabolism Neuronal Plasticity/drug effects,genetics Neuroprotective Agents/metabolism,therapeutic use Primates Receptors, Estrogen/genetics,metabolism Rodentia Signal Transduction/drug effects,genetics Tropism/drug effects,genetics
Chemicals
Estrogens Neuroprotective Agents Receptors, Estrogen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Brann Darrell W
Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta, GA 30912, United States. [email protected]
Dhandapani Krishnan
Wakade Chandramohan
Mahesh Virendra B
Khan Mohammad M
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Article Info
Journal
Steroids
Abbr.
Steroids
ISSN
0039-128X
DOI
10.1016/j.steroids.2007.02.003
Email
[email protected]
Published
2007-05-00
Epub
2007-00-21
Pages
381-405
Language
English
Region
United States
NLM ID
0404536
PMCID
PMC2048656
Subset
IM
Grants
NINDS NIH HHS · R01 NS050730 · United States
NICHD NIH HHS · HD28965 · United States
NINDS NIH HHS · NS050730 · United States
External Links
PubMed source DOI: 10.1016/j.steroids.2007.02.003 PMC Full Text View journal details
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