Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors α and β

Neurogenesis persists throughout life under normal and degenerative conditions. The adult subventricular zone (SVZ) generates neural stem cells capable of differentiating to neuroblasts and migrating to the site of injury in response to brain insults. In the present study, we investigated whether es...

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Bibliographic Details
Published in:Journal of comparative neurology (1911) 2007-02, Vol.500 (6), p.1064-1075
Main Authors: Suzuki, Shotaro, Gerhold, Lynnette M., Böttner, Martina, Rau, Shane W., Dela Cruz, Christopher, Yang, Enhua, Zhu, Hong, Yu, Jin, Cashion, Adrienne B., Kindy, Mark S., Merchenthaler, Istvan, Gage, Fred H., Wise, Phyllis M.
Format: Article
Language:English
Subjects:
Animals
Brain Ischemia - etiology
Brain Ischemia - metabolism
Brain Ischemia - pathology
BrdU
Cell Count
Cerebral Ventricles - cytology
Cerebral Ventricles - metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Estradiol - administration & dosage
Estradiol - metabolism
estrogen receptor
Estrogen Receptor alpha - metabolism
Estrogen Receptor beta - metabolism
estrogen receptor, immunocytochemistry
Female
immunocytochemistry
ischemia
Matched-Pair Analysis
Mice
Mice, Inbred C57BL
Mice, Knockout
neural stem cells
Neurons - cytology
Neurons - metabolism
Neuroprotective Agents - administration & dosage
Neuroprotective Agents - metabolism
Stem Cells - cytology
Stem Cells - metabolism
stroke
Stroke - complications
Stroke - metabolism
Stroke - pathology
subventricular zone
Time Factors
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Summary:Neurogenesis persists throughout life under normal and degenerative conditions. The adult subventricular zone (SVZ) generates neural stem cells capable of differentiating to neuroblasts and migrating to the site of injury in response to brain insults. In the present study, we investigated whether estradiol increases neurogenesis in the SVZ in an animal model of stroke to potentially promote the ability of the brain to undergo repair. Ovariectomized C57BL/6J mice were implanted with capsules containing either vehicle or 17β‐estradiol, and 1 week later they underwent experimental ischemia. We utilized double‐label immunocytochemistry to identify the phenotype of newborn cells (5‐bromo‐2′‐deoxyuridine‐labeled) with various cellular markers; doublecortin and PSA‐NCAM as the early neuronal marker, NeuN to identify mature neurons, and glial fibrillary acidic protein to identify astrocytes. We report that low physiological levels of estradiol treatment, which exert no effect in the uninjured state, significantly increase the number of newborn neurons in the SVZ following stroke injury. This effect of estradiol is limited to the dorsal region of the SVZ and is absent from the ventral SVZ. The proliferative actions of estradiol are confined to neuronal precursors and do not influence gliosis. Furthermore, we show that both estrogen receptors α and β play pivotal functional roles, insofar as knocking out either of these receptors blocks the ability of estradiol to increase neurogenesis. These findings clearly demonstrate that estradiol stimulates neurogenesis in the adult SVZ, thus potentially facilitating the brain to remodel and repair after injury. J. Comp. Neurol. 500:1064–1075, 2007. © 2006 Wiley‐Liss, Inc.
ISSN:0021-9967
1096-9861
DOI:10.1002/cne.21240