TY - JOUR
T1 - Neurotrophic and neuroprotective actions of estrogen
T2 - Basic mechanisms and clinical implications
AU - Brann, Darrell W
AU - Dhandapani, Krishnan Michael
AU - Wakade, Chandramohan G.
AU - Mahesh, Virendra B.
AU - Khan, Mohammad M.
N1 - Funding Information:
This research was supported by Research Grants (HD28965 and NS050730) from the National Institute of Child Health and Human Development, and National Institutes of Neurological Disorders and Stroke, National Institutes of Health.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Estrogen
KW - Neuroprotection
KW - Parkinson disease
KW - Stroke
KW - Synaptic plasticity
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U2 - 10.1016/j.steroids.2007.02.003
DO - 10.1016/j.steroids.2007.02.003
M3 - Review article
C2 - 17379265
AN - SCOPUS:34247150317
SN - 0039-128X
VL - 72
SP - 381
EP - 405
JO - Steroids
JF - Steroids
IS - 5
ER -