Estrogen and Bcl-2: Gene induction and effect of transgene in experimentalstroke

Citation
Nj. Alkayed et al., Estrogen and Bcl-2: Gene induction and effect of transgene in experimentalstroke, J NEUROSC, 21(19), 2001, pp. 7543-7550
Citations number
46
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
02706474 → ACNP
Volume
21
Issue
19
Year of publication
2001
Pages
7543 - 7550
Database
ISI
SICI code
0270-6474(20011001)21:19<7543:EABGIA>2.0.ZU;2-Q
Abstract
Female rodents producing endogenous estrogens are protected from stroke dam age in comparison with male counterparts. This natural protection is lost a fter ovariectomy or reproductive senescence. The aim of this study is to de termine whether estrogen reduces early neuronal injury and cell loss after ischemia by increasing the expression of Bcl-2. Male, intact female, ovarie ctomized, and estrogen-repleted ovariectomized rats were subjected to middl e cerebral artery occlusion, and 22 hr later the level and localization of Bcl-2 mRNA and protein were determined. The levels of post-ischemic bcl-2 m RNA and protein were increased exclusively in neurons within the peri-infar ct region. Intact females and estrogen-treated castrates demonstrated incre ased bcl-2 mRNA and protein expression compared with males and estrogen-def icient females, accompanied by a decrease in infarct size. To test the hypo thesis that the neuroprotective mechanism of estrogen functions via Bcl-2, we compared ischemic outcome in male, female, and ovariectomized wild-type mice and mice overexpressing Bcl-2 exclusively in neurons. Wild-type female mice sustained smaller infarcts compared with males. Bcl-2 overexpression reduced infarct size in males, but provided no added protection in the fema le. Moreover, ovariectomy exacerbated infarction in wildtype females, but h ad no effect in Bcl-2 overexpressors. These data indicate that overexpressi on of Bcl-2 simulates the protection against ischemic injury conferred by e ndogenous female sex steroids. We concluded that estrogen rescues neurons a fter focal cerebral ischemia by increasing the level of Bcl-2 in peri-infar ct regions and that estrogen-induced bcl-2 gene expression is an important downstream component of neuronal protection in female stroke.