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.

by Darrell W. Brann,*1,2,3 Krishnan Dhandapani,1,2,4 Chandramohan Wakade,1 Virendra B. Mahesh,1 and Mohammad M. Khan1,2


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 WHI (Women’s Health Initiative) 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.


www.pubmedcentral.nih.gov

Steroids. Author manuscript; available in PMC 2007 November 1.

Published in final edited form as:  Steroids. 2007 May; 72(5): 381–405.

Published online 2007 February 21. doi: 10.1016/j.steroids.2007.02.003.

 

Footnotes

1. Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta, GA 30912

2. Institute of Neuroscience, School of Medicine, Medical College of Georgia, Augusta, GA 30912

3. Department of Neurology, School of Medicine, Medical College of Georgia, Augusta, GA 30912

4. Department of Neurosurgery, School of Medicine, Medical College of Georgia, Augusta, GA 30912