ESTROGEN ATTENUATES OVER-EXPRESSION OF BETA-AMYLOID PRECURSOR PROTEINMESSENGER-RNA IN AN ANIMAL-MODEL OF FOCAL ISCHEMIA

Cerebral ischemia is a risk factor for late onset Alzheimer's disease. Since estrogen replacement therapy benefits the outcome of cerebral s troke in post-menopausal women, we designed the present study to inves tigate the effects of estrogen on the expression of beta-amyloid precu rsor protein (APP) mRNA following focal ischemia in female rats. Femal e rats were ovariectomized (OVX) for two weeks. A single dose of 17 be ta-estradiol (E-2) (100 mu g/kg) was injected s.c. two hours before a unilateral middle cerebral artery (MCA) occlusion. Brain samples were harvested from ischemic core and penumbra of cortices at one hour and twenty-four hours following MCA occlusion. The expression of APP mRNA was assessed by RT-PCR. At one hour after MCA occlusion, OVX rats had a 67.9% (p < 0.05) increase in APP mRNA in the penumbra. E-2 treatment reduced this APP mRNA over-expression by 26.3% at that region. At twe nty four hours following MCA occlusion, OVX rats had increases in APP mRNA of 52.9% and 57.0% (p < 0.05) in the core and penumbra, respectiv ely. E-2 treatment reduced the APP mRNA over-expression by 61.0% and 4 8.6% (p < 0.05) in these two regions, respectively. These effects appe ared to reflect an interaction between hormonal environment and ischem ia, since in the absence of MCA occlusion, there were no significant d ifferences in APP mRNA expression among OVX, OVX-E-2 treated and intac t female rats. The present study demonstrates that estrogen may have a n important role in reducing the over-expression of APP mRNA following focal ischemia. (C) 1998 Elsevier Science B.V. All rights reserved.