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Brain region‐specific up‐regulation of mouse apolipoprotein E by pharmacological estrogen treatments
Author(s) -
LevinAllerhand Justine,
McEwen Bruce S.,
Lominska Chris E.,
Lubahn Dennis B.,
Korach Kenneth S.,
Smith Jonathan D.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00627.x
Subject(s) - endocrinology , medicine , apolipoprotein e , estrogen , ovariectomized rat , diencephalon , hippocampus , estrogen receptor , cerebral cortex , estrogen receptor beta , biology , agonist , hypothalamus , receptor , disease , cancer , breast cancer
Cerebral apolipoprotein E (apoE) has been implicated in neuronal protection and repair. Due to the variable levels and types of estrogen receptors within different brain regions, the effect of estrogen on apoE and the mechanism of this effect may vary within different regions. Ovariectomized female C57BL/6 mice were treated with pharmacological levels of 17β‐estradiol or placebo for 5 days, resulting in supraphysiological plasma levels of estradiol in the treated mice. ApoE and glial fibrillary acidic protein (GFAP) levels were measured in the cortex, hippocampus and diencephalon. 17β‐Estradiol up‐regulated apoE but not GFAP in the cortex and diencephalon, whereas in the hippocampus, GFAP and apoE were equally up‐regulated. Treatment of estrogen receptor (ER) α knockout mice with 17β‐estradiol or treatment of C57BL/6 mice with 17α‐estradiol, a poor estrogen receptor agonist, specifically induced apoE in the cortex, but not in the diencephalon. These results indicate that 17β‐estradiol effects on apoE are either directly or indirectly mediated by ERα in the diencephalon, while the effects in the cortex may be mediated by a non‐classical mechanism or by ERβ. Measurement of mRNA levels in estrogen versus placebo‐treated wild‐type mice indicated that the effect of 17β‐estradiol on apoE was not associated with changes in apoE mRNA levels.