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Alzheimer's Aβ1–40 Peptide Modulates Lipid Synthesis in Neuronal Cultures and Intact Rat Fetal Brain Under Normoxic and Oxidative Stress Conditions

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Abstract

The effect of amyloid β (Aβ), the major constituent of the Alzheimer's (AD) brain on lipid metabolism was investigated in cultured nerve cells and in a fetal rat brain model. Differentiated (NGF) and undifferentiated PC12 cells or primary cerebral cell cultures were incubated with [14C]acetate in the absence or presence of Aβ1–40. Incorporation of label into lipid species was determined after lipid extraction and TLC separation. Phosphatidylcholine (PC) and phosphatidylserine (PS) synthesis was increased by Aβ1–40, in a dose dependent manner, an effect which was more pronounced in differentiated PC12 cells. A significant proportion of radioactivity (5–6%) was released into the medium with a radioactivity distribution similar to that of the cellular lipids. Cholesterol and PC were the highest labeled medium lipids. Increasing Aβ1–40 concentration up to 0.1 μg/ml in cerebral cells but not in PC12 cells, caused a relative increase (1.5 fold) in release of PS, while that of PE decreased. Stimulation of PS release may possibly be associated with apoptotic cell death. Aβ1–40 peptide (5 μg) was administered intraperitonealy into rat fetuses (18 days gestation) along with [14C]acetate (2μCi/fetus). After 24 h, the maternal-fetal blood supply was occluded for 20 min (ischemia) followed by 15 min reperfusion. Fetuses were killed and liver and brain tissue subjected to lipid extraction and radioactivity determination after TLC. Aβ1–40 peptide increased synthesis of different classes of lipids up to 20–40% in brain tissue compared to controls. Labeling of liver lipids was decreased by Aβ1–40 by 20–30%. A general decrease in synthesis of lipids was observed after ischemia/reperfusion. Our data suggest that Aβ1–40 peptide regulates normal lipid biosynthesis but under ischemia it compromises it. The latter finding may confirm the oxidative stress etiology in AD and suggests that Aβ1–40 modulation of lipid metabolism may have Alzheimer's pathological relevance, particularly at high peptide concentrations.

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Authors and Affiliations

  1. Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Natalia V. Koudinova & Alexei R. Koudinov

  2. Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Ephraim Yavin

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  2. Alexei R. Koudinov
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Koudinova, N.V., Koudinov, A.R. & Yavin, E. Alzheimer's Aβ1–40 Peptide Modulates Lipid Synthesis in Neuronal Cultures and Intact Rat Fetal Brain Under Normoxic and Oxidative Stress Conditions. Neurochem Res 25, 653–660 (2000). https://doi.org/10.1023/A:1007511120099

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