Title
LDL receptor deficiency results in decreased cell proliferation and presynaptic bouton density in the murine hippocampus
Author
Mulder, M.
Koopmans, G.
Wassink, G.
Mansouri, G.A.
Simard, M.-L.
Havekes, L.M.
Prickaerts, J.
Blokland, A.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
An aberrant cholesterol metabolism in the brain may contribute to the pathogenesis of Alzheimer's disease (AD). The LDL receptor (LDLR) regulates plasma cholesterol levels and recently we and others obtained evidence that it is also involved in regulating brain cholesterol homeostasis. Moreover, we found that LDLR-deficient mice display impaired spatial memory. Because cholesterol, in part derived from cellular uptake via LDLR, is required for peripheral cell proliferation and growth, we examined the effect of absence of the LDLR on hippocampal proliferation and the density of synaptic connections. Mice deficient for the LDLR displayed a reduced number of proliferating (BrdU-labeled) cells in the hippocampus as compared to wild type control mice. In addition, the number of synaptophysin-immunoreactive presynaptic boutons in the hippocampal CA1 and the dentate gyrus (DG) areas, but not in cortical areas, was lower in the LDLR-knockout mice than in the control mice. In vitro experiments showed that LDLR activity is increased when cell growth is enhanced by the addition of N2 supplement. This further supports a role for the LDLR in the outgrowth of neurites. These findings support the notion that, similar to its role in the periphery, the LDLR is important for the cellular uptake of cholesterol in the brain and that disturbance of this process affects neuronal plasticity. © 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society.
Subject
Health
Biomedical Research
Apolipoprotein E
Cholesterol
Low density lipoprotein receptor
Memory
Neurogenesis
Synaptic density
apolipoprotein E
broxuridine
cholesterol
iodine 125
low density lipoprotein
low density lipoprotein receptor
synaptophysin
Alzheimer disease
animal cell
animal experiment
animal tissue
article
astrocytoma cell
cell proliferation
cholesterol metabolism
concentration response
controlled study
dentate gyrus
hippocampus
knockout mouse
male
memory
mouse
nerve cell plasticity
nerve fiber growth
nervous system development
neuroblastoma cell
nonhuman
pathogenesis
priority journal
spatial memory
synaptogenesis
wild type
Animals
Biological Markers
Bromodeoxyuridine
Cell Count
Cell Line, Tumor
Cell Proliferation
Cholesterol
Dentate Gyrus
Down-Regulation
Hippocampus
Humans
Male
Mice
Mice, Knockout
Neural Pathways
Neuronal Plasticity
Presynaptic Terminals
Receptors, LDL
Synaptophysin
To reference this document use:
http://resolver.tudelft.nl/uuid:b3ed8a3a-2f01-48f7-99f6-04c55bd2c30d
DOI
https://doi.org/10.1016/j.neures.2007.07.004
TNO identifier
240266
ISSN
0168-0102
Source
Neuroscience Research, 59 (3), 251-256
Document type
article