PMID- 18503570
OWN - NLM
STAT- MEDLINE
DCOM- 20090219
LR  - 20211020
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 19
IP  - 1
DP  - 2009 Jan
TI  - Activity-regulated cytoskeleton-associated protein in rodent brain is 
      down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro.
PG  - 69-80
LID - 10.1111/j.1750-3639.2008.00174.x [doi]
AB  - Growing evidence strongly suggests that high fat diet (HFD) has an important role 
      in some neurodegenerative disorders, including Alzheimer's disease (AD). To 
      identify new cellular pathways linking hypercholesterolemia and 
      neurodegeneration, we analyzed the effects of HFD on gene expression in mouse 
      brain. Using cDNA microarrays and real time RT-PCR, we found that HFD has a mild, 
      but significant effect on the expression of several genes. The altered genes 
      include molecules linked to AD pathology and others of potential interest for 
      neurodegeneration. We further investigated the effect of HFD on the 
      activity-regulated cytoskeleton-associated protein (Arc). Expression of Arc was 
      decreased in cerebral cortex and hippocampus of HFD-fed animals. From the known 
      regulatory mechanisms of Arc expression, HFD reduced N-methyl-D-aspartate 
      receptor (NMDAR) activity, as seen by decreases in tyrosine phosphorylation of 
      NMDAR2A and levels of NMDAR1. Additionally, we demonstrated that 
      27-hydroxycholesterol, a cholesterol metabolite that enters the brain from the 
      blood, decreases Arc levels as well as NMDAR and Src kinase activities in rat 
      primary hippocampal neurons. Finally, we showed that Arc levels are decreased in 
      the cortex of AD brains. We propose that one of the mechanisms, by which 
      hypercholesterolemia contributes to neurodegenerative diseases, could be through 
      Arc down-regulation caused by 27-hydroxycholesterol.
FAU - Mateos, Laura
AU  - Mateos L
AD  - Department of Neurobiology, Care Sciences and Society, Karolinska 
      Institutet-Alzheimer's Disease Research Center, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Akterin, Susanne
AU  - Akterin S
FAU - Gil-Bea, Francisco-Javier
AU  - Gil-Bea FJ
FAU - Spulber, Stefan
AU  - Spulber S
FAU - Rahman, Atiqur
AU  - Rahman A
FAU - Bjorkhem, Ingemar
AU  - Bjorkhem I
FAU - Schultzberg, Marianne
AU  - Schultzberg M
FAU - Flores-Morales, Amilcar
AU  - Flores-Morales A
FAU - Cedazo-Minguez, Angel
AU  - Cedazo-Minguez A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080523
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (ARHGEF26 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Dietary Fats)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (SGEF protein, mouse)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - 113-79-1 (Arginine Vasopressin)
RN  - 63231-63-0 (RNA)
RN  - 6T2NA6P5SQ (27-hydroxycholesterol)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Arginine Vasopressin/genetics
MH  - Brain/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Cytoskeletal Proteins/*metabolism
MH  - Dietary Fats/administration & dosage/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Guanine Nucleotide Exchange Factors/genetics
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Hydroxycholesterols/pharmacology
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA/genetics/metabolism
MH  - Receptors, Glutamate/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - src-Family Kinases/metabolism
PMC - PMC8095555
EDAT- 2008/05/28 09:00
MHDA- 2009/02/20 09:00
PMCR- 2008/05/23
CRDT- 2008/05/28 09:00
PHST- 2008/05/28 09:00 [entrez]
PHST- 2008/05/28 09:00 [pubmed]
PHST- 2009/02/20 09:00 [medline]
PHST- 2008/05/23 00:00 [pmc-release]
AID - BPA174 [pii]
AID - 10.1111/j.1750-3639.2008.00174.x [doi]
PST - ppublish
SO  - Brain Pathol. 2009 Jan;19(1):69-80. doi: 10.1111/j.1750-3639.2008.00174.x. Epub 
      2008 May 23.