S100β Increases Levels of β-Amyloid Precursor Protein and Its Encoding mRNA in Rat Neuronal Cultures |
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Authors: | Yuekui Li,Jianzhong Wang,&dagger Jin G. Sheng,Ling Liu,&Dagger § Steven W. Barger,&Dagger § Richard A. Jones,¶ Linda J. Van Eldik,§ #Robert E. Mrak, &Dagger § W. Sue T. Griffin |
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Affiliation: | Departments of Geriatrics,; Pathology, and; Anatomy, University of Arkansas Medical Sciences, and; Geriatric Research Education and Clinical Center,; Veterans' Affairs Medical Center, Little Rock, Arkansas, and; Northwestern Drug Discovery Program and Department of Cell and Molecular Biology and Biochemistry, Northwestern University, Chicago, Illinois, U.S.A.;and; Department of Neurology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai, People's Republic of China |
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Abstract: | Abstract: S100β has been implicated in the formation of dystrophic neurites, overexpressing β-amyloid precursor protein (βAPP), in the β-amyloid plaques of Alzheimer's disease. We assessed the effects of S100β on cell viability of, neurite outgrowth from, and βAPP expression by neurons in primary cultures from fetal rat cortex. S100β (1–10 ng/ml) enhanced neuronal viability (as assessed by increased mitochondrial activity and decreased lactic acid dehydrogenase release) and promoted neurite outgrowth. Higher levels of S100β (100 ng/ml, but not 1 µg/ml) produced qualitatively similar, but less marked, effects. S100β also induced increased neuronal expression of the microtubule-associated protein MAP2, an effect that is consistent with trophic effects of S100β on neurite outgrowth. S100β (10 and 100 ng/ml) induced graded increases in neuronal expression of βAPP and of βAPP mRNA. These results support our previous suggestion that excessive expression of S100β by activated, plaque-associated astrocytes in Alzheimer's disease contributes to the appearance of dystrophic neurites overexpressing βAPP in diffuse amyloid deposits, and thus to the conversion of these deposits into the diagnostic neuritic β-amyloid plaques. |
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Keywords: | Alzheimer's disease β-Amyloid precursor protein In situ hybridization Northern hybridization S100β Western immunoblot |
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