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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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