Title
Human apolipoprotein C-I expression in mice impairs learning and memory functions
Author
Abildayeva, K.
Berbée, J.F.P.
Blokland, A.
Jansen, P.J.
Hoek, F.J.
Meijer, O.
Lütjohann, D.
Gautier, T.
Pillot, T.
de Vente, J.
Havekes, L.M.
Ramaekers, F.C.S.
Kuipers, F.
Rensen, P.C.N.
Mulder, M.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD brains. Interestingly, apoC-I colocalized with β-amyloid (Aβ) in plaques in AD brains, and in vitro experiments revealed that aggregation of Aβ was delayed in the presence of apoC-I. Moreover, apoC-I was found to exacerbate the soluble Ab oligomer-induced neuronal death. To establish a potential role for apoC-I in cognitive functions, we used human (h) APOC1+/0 transgenic mice that express APOC1 mRNA throughout their brains and apoC-I protein in astrocytes and endothelial cells. The hAPOC1+/0 mice displayed impaired hippocampal-dependent learning and memory functions compared with their wild-type litter- mates, as judged from their performance in the object recognition task (P = 0.012) and in the Morris water maze task (P = 0.010). ApoC-I may affect learning as a result of its inhibitory properties toward apoE-dependent lipid metabolism. However, no differences in brain mRNA or protein levels of endogenous apoE were detected between transgenie and wild-type mice. Copyright © 2008 by the American Society for Biochemistry and Molecular Biology, Inc.
Subject
Health
Physiological Sciences
β-amyloid
Alzheimer's disease
Apolipoprotein E
Morris water maze task
Object recognition task
amyloid beta protein
apolipoprotein E
campesterol
cholestanol
cholesterol
cholesterol derivative
desmosterol
lanosterol
lathosterol
lysophosphatidylcholine
lysophosphatidylethanolamine
messenger RNA
phosphatidylcholine
phosphatidylethanolamine
phosphatidylinositol
phosphatidylserine
sitosterol
sphingomyelin
unclassified drug
animal cell
animal experiment
animal model
animal tissue
apoptosis
astrocyte
brain level
cell viability
controlled study
disease exacerbation
endothelium cell
female
hippocampus
human tissue
learning disorder
lipid metabolism
maze test
memory disorder
mouse
nerve cell necrosis
nonhuman
protein aggregation
protein expression
recognition
task performance
transgenic mouse
wild type
animal
C57BL mouse
gene expression regulation
genetics
metabolism
Animals
Apolipoprotein C-I
Gene Expression Regulation
Humans
Immunohistochemistry
Learning
Memory
Mice
Mice, Inbred C57BL
Mice, Transgenic
RNA, Messenger
Tissue Culture Techniques
To reference this document use:
http://resolver.tudelft.nl/uuid:9e5eb2a3-1b96-400b-9d1b-2947844ca0fa
DOI
https://doi.org/10.1194/jlr.m700518-jlr200
TNO identifier
240744
ISSN
0022-2275
Source
Journal of Lipid Research, 49 (4), 856-869
Document type
article