ALZHEIMER'S AMYLOID BETA MODULATES LIPID SYNTHESIS IN RAT HIPPOCAMPUS

N.V. Koudinova^1,2*; A.R. Koudinov^1,2; T.T. Berezov^1,2 and E. Yavin¹

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

2. Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation

Membrane destabilization in Alzheimer's disease (AD) may be a consequence of altered lipid composition modulated by amyloid beta protein (Ab) (FASEB J 1998, 12: 1097). The effect of Ab on lipid synthesis in adult rat hippocampal slices (400 m), expressing normal synaptic physiology and long term potentiation as assessed by extracellular recording in the CA1, was examined. Slices were labeled for 21 h with [14C]-acetate (0.1 mCi/ml of artificial cerebrospinal fluid, aCSF) in the absence or presence of Ab1-40 (0.33 mg/ml). After labeling, lipids were extracted by hexane:isopropanol (3:2 v/v), separated on thin layer chromatography, and radioactive lipid bands scrapped off the silica gel plates and counted. Ab1-40 increased synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and cholesterol (Chl) by 33, 67 and 46 % above the control values, respectively. Slices treated with Ab showed two fold [14C]-acetate incorporation into lipids in the CA1 pyramidal cell layer over untreated slices, as revealed by autoradiography. To test whether stimulation of slices attenuates the effect of Ab, KCl (50 mM) was added to aCSF for 2.5 min, followed by metabolic labeling of lipids in regular aCSF containing 2 mM KCl. Under these conditions Ab decreased the synthesis of PC and PE by ~29 % and ~34 %, respectively, but not synthesis of Chl. Our data suggest that Ab modulation of adult hippocampal lipid synthesis i) is dependent on neuronal physiological status, and ii) may be of value in understanding neurodegeneration and AD pathophysiology.

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