Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus.
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.
Mulder
Monique
M
Department of Molecular Cell Biology, Maastricht University and University Hospital Maastricht, Maastricht, The Netherlands. M.Mulder@MOLCELB.unimaas.nl
Jansen
Paula J
PJ
Janssen
Ben J A
BJ
van de Berg
Wilma D J
WD
van der Boom
Hans
H
Havekes
Louis M
LM
de Kloet
Ron E
RE
Ramaekers
Frans C S
FC
Blokland
Arjan
A
D000818:Animals; D002452:Cell Count / Q000379:methods; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D011973:Receptors, LDL