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Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus

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Author: Mulder, M. · Jansen, P.J. · Janssen, B.J.A. · Berg, W.D.J. van de · Boom, H. van der · Havekes, L.M. · Kloet, R.E. de · Ramaekers, F.C.S. · Blokland, A.
Type:article
Date:2004
Institution: TNO Preventie en Gezondheid
Source:Neurobiology of Disease, 1, 16, 212-219
Identifier: 280227
doi: doi:10.1016/j.nbd.2004.01.015
Keywords: Environment · Alzheimer's disease · Apolipoprotein E · Lipid metabolism · Low-density lipoprotein receptor family · Memory · Low density lipoprotein receptor · Synaptophysin · Animal experiment · Animal model · Animal tissue · Atherosclerosis · Controlled study · Hippocampus · Homozygosity · Knockout mouse · Maze test · Memory disorder · Mouse · Nerve ending · Nonhuman · Spatial memory · Task performance · Wild type · Working memory · Animals · Cell Count · Hippocampus · Male · Maze Learning · Memory Disorders · Mice · Mice, Inbred C57BL · Mice, Knockout · Presynaptic Terminals · Receptors, LDL · Synapses

Abstract

The low-density lipoprotein receptor (LDLR) is the first described receptor for apolipoprotein E (apoE). We hypothesize that the absence of the LDLR, similar to the absence of apoE, results in impaired learning and memory processes. Six-month-old homozygous Ldlr-/- and wild-type littermates (Ldlr+/+), maintained on a standard lab chow diet, were used. Unlike humans, Ldlr-/- mice, under these conditions, do not develop atherosclerosis. The results of the Morris water escape task revealed an impaired spatial memory in the Ldlr-/- mice in comparison with Ldlr+/+ mice. Also in a T-maze task, the working memory performance of the Ldlr-/- mice was impaired. Furthermore, Ldlr-/- mice, in comparison with Ldlr+/+ mice, display a decreased number of synaptophysin- immunoreactive presynaptic boutons in the hippocampus CA1. In conclusion, the results show in mice deficiency for the LDLR results in impaired hippocampal-dependent memory functions. A decrease in the number of presynaptic boutons may underlay these behavioral alterations. Therefore, the LDLR may be an important receptor for apoE in the central nervous system. © 2004 Elsevier Inc. All rights reserved. Chemicals/CAS: Receptors, LDL