Apolipoprotein E4 enhances brain inflammation by modulation of the NF-kappaB signaling cascade

Autor: Gal Ophir, Daniel M. Michaelson, Ran Elkon, Gideon Rechavi, Ninette Amariglio, Jasmine Jacob-Hirsch
Rok vydání: 2005
Předmět:
Genetically modified mouse
Apolipoprotein E
Lipopolysaccharides
Male
Transcriptional Activation
medicine.medical_specialty
LPS
Transgene
Apolipoprotein E4
Apolipoprotein E3
Inflammation
Mice
Transgenic
Microarray
Biology
Hippocampal formation
NF-κB
lcsh:RC321-571
Mice
Apolipoproteins E
Alzheimer Disease
Internal medicine
mental disorders
Gene expression
medicine
Animals
Humans
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Injections
Intraventricular
Gene Expression Profiling
NF-kappa B
Brain
Alzheimer's disease
Molecular biology
Up-Regulation
Gene expression profiling
Disease Models
Animal
Endocrinology
Neurology
Gene Expression Regulation
Multigene Family
Encephalitis
lipids (amino acids
peptides
and proteins)
medicine.symptom
Signal transduction
human activities
Signal Transduction
Zdroj: Neurobiology of Disease, Vol 20, Iss 3, Pp 709-718 (2005)
ISSN: 0969-9961
Popis: Apolipoprotein E4 (apoE4), the major genetic risk factor of Alzheimer's disease (AD), is associated with enhanced brain inflammation. Genome-wide gene expression profiling was employed to study the effects of apoE genotype on hippocampal gene expression in LPS-treated mice, transgenic for either apoE4 or the AD benign allele, apoE3. This revealed that the expression of inflammation-related genes following intracerebroventricular injection of LPS was significantly higher and more prolonged in apoE4 than in apoE3 transgenic mice. Clustering analysis revealed gene clusters which responded differently in apoE4 and apoE3 mice and were significantly enriched in NF-kappaB response elements. Direct measurement of NF-kappaB-regulated genes revealed that their extent of activation was greater in the apoE4 mice. Immunohistochemistry experiments revealed that microglial and NF-kappaB activation were more pronounced in apoE4 than in apoE3 mice. These findings suggest that the increased brain inflammation in apoE4 mice is related to disregulation of NF-kappaB signaling pathway.
Databáze: OpenAIRE
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