RGD Reference Report - Suppression of central chemokine fractalkine receptor signaling alleviates amyloid-induced memory deficiency. - Rat Genome Database

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Suppression of central chemokine fractalkine receptor signaling alleviates amyloid-induced memory deficiency.

Authors: Wu, J  Bie, B  Yang, H  Xu, JJ  Brown, DL  Naguib, M 
Citation: Wu J, etal., Neurobiol Aging. 2013 Dec;34(12):2843-52. doi: 10.1016/j.neurobiolaging.2013.06.003. Epub 2013 Jul 12.
RGD ID: 9491766
Pubmed: (View Article at PubMed) PMID:23855980
DOI: Full-text: DOI:10.1016/j.neurobiolaging.2013.06.003

The abnormal accumulation of amyloid fibrils in the brain is pathognomonic of Alzheimer's disease. Amyloid fibrils induce significant neuroinflammation characterized by the activation of microglia and impairment of synaptic plasticity in the brain that eventually leads to cognitive decline. Chemokine fractalkine receptor (CX3CR1) is primarily located in the microglia in the brain and its role in the amyloid fibril-induced neuroinflammation and memory deficiency remains debated. We found that bilateral microinjection of amyloid beta (Abeta)1-40 fibrils into the hippocampal CA1 area of rats resulted in significant upregulation of CX3CR1 messenger RNA (mRNA) and protein expression (via increasing histone H3 acetylation in the Cx3cr1 promoter region), synaptic dysfunction, and cognitive impairment, compared with the control group. Suppressing CX3CR1 signaling with CX3CR1 small interfering RNA in rats injected with Abeta1-40 fibrils blunted Abeta1-40-induced CX3CR1 upregulation, microglial activation, interleukin-1beta expression, restored basal glutamatergic strength and electric stimuli-induced long-term potentiation, and cognitive capacities. These findings suggest that activation of CX3CR1 plays an important role in the neuroinflammatory response and Abeta-induced neuroinflammation and neurotoxicity.

Disease Annotations    
Memory Disorders  (IMP,ISO)

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Mus musculus)
Cx3cr1  (chemokine (C-X3-C motif) receptor 1)

Genes (Homo sapiens)
CX3CR1  (C-X3-C motif chemokine receptor 1)

Additional Information