Premium
Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors α and β
Author(s) -
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.
Publication year - 2006
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21240
Subject(s) - neurogenesis , doublecortin , neun , subventricular zone , biology , neuroblast , glial fibrillary acidic protein , neural stem cell , neuroscience , estrogen receptor , gliosis , endocrinology , medicine , microbiology and biotechnology , stem cell , hippocampus , dentate gyrus , immunology , immunohistochemistry , cancer , breast cancer , genetics
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.