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Essential Role for Cholesterol in Synaptic Plasticity and Neuronal Degeneration

Alexei R. Koudinov 1,2,3  and Natalia V. Koudinova 1,2

1 Weizmann Institute of Science, Department of Biological Regulation, Rehovot, 76100 Israel;
2 Institute of Biomedical Chemistry and 3 National Mental Health Research Center, Russian Academy of Medical Sciences, Timoshenko St., 38-27, Moscow, 121359 Russia;

Corresponding author:  Alexei R. Koudinov, M.D., Ph.D., P.O.Box 1665, Rehovot 76100 Israel; Tel:  (972 54) 796-8607 ; Email | Web address 1 | 2 | 3

ABSTRACT

There is no understanding of the role of cholesterol and phospholipids in the mechanisms of synaptic function and neurodegeneration. Here we report that cholesterol disbalance is critical for synaptic transmission and plasticity as investigated by a study of paired pulse facilitation (PPF) and long-term potentiation (LTP). Extracellular recording of field evoked postsynaptic potentials showed enhanced PPF ratio and an impairment of LTP in CA1 subfield of adult rat ex-vivo hippocampal slices subjected to cyclodextrin- or normal human CSF-HDL3-mediated cholesterol efflux. Immunofluorescence with antibodies against neurofilament and tau revealed that cholesterol and phospholipids depletion causes alteration of normal hippocampal neurites and the appearance of PHF-tau in the mossy fibers. We further find that LTP and amyloid beta protein increase [14C]acetate label incorporation into newly synthesized hippocampal membrane lipids. Our results indicate importance of neuronal cholesterol redistribution and synthesis for synaptic plasticity and neurodegeneration. 
Keywords: Amyloid beta protein, Alzheimer’s disease, Down’s syndrome, cholesterol and phospholipid efflux and synthesis, hippocampal slices, lipoprotein LDL LRP VLDL receptor, Niemann-Pick type C disease, NFT tau phosphorylation

Originally peer reviewed and published online by FASEB Journal (27 June 2001)  doi:10.1096/fj.00-0815fje , http://www.fasebj.org/cgi/content/short/00-0815fjev1 . 

The short version of this article is available as FJ Express Summary article (The FASEB Journal 2001;15:1858-1860, 
http://www.fasebj.org/cgi/content/full/15/10/1858

Original Publication Citation: AR Koudinov, NV Koudinova. Essential Role for Cholesterol in Synaptic Plasticity and Neuronal Degeneration. FAEB Journal (27 June 2005) doi:10.1096/fj.00-0815fje, Vol. 15, 8, 1858-1860 [Publisher Abstract][Publisher FullText .PDF][FASEB J Express Summary]

Israel Scholar Works Citation: AR Koudinov, NV Koudinova. Essential Role for Cholesterol in Synaptic Plasticity and Neuronal Degeneration. Israel Scholar Works (14 October 2006) Vol. 1, 1, http://israelscholar.org/content/1/1
 

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