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- Title
Memory deficits and neurochemical changes induced by C-reactive protein in rats: implication in Alzheimer’s disease.
- Authors
Lin, Huan-Bing; Yang, Xue-Mei; Li, Tie-Jun; Cheng, Yu-Fang; Zhang, Han-Ting; Xu, Jiang-Ping
- Abstract
C-reactive protein (CRP), an acute phase protein that is released in response to inflammatory stimuli, is implicated in Alzheimer's disease (AD). However, the role of CRP in memory deficits associated with AD remains unclear. Experiments were carried out to determine whether CRP impaired memory and altered neurochemical measures associated with AD. The effects of intra-cerebroventricular administration of CRP or β-amyloid peptide 25–35 (Aβ25–35) on memory performance were evaluated using rat Morris water-maze and step-through passive avoidance tests; the levels of inflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor (TNF-α)), endogenous CRP, and markers of the endogenous production of Aβ, including amyloid precursor protein (APP), presenilins (PS-1 and PS-2), and β-site of APP cleaving enzyme (BACE), were also determined in brain regions using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting analysis. Treatment with CRP (25.6 μg/rat) or Aβ25-35 (10 μg/rat) 2 weeks ahead produced impairment of long-term memory in both animal tests. Real-time RT-PCR revealed increases in messenger RNA levels of APP, IL-1β, IL-6, TNF-α, and CRP in the cerebral cortex and hippocampus and those of PS-1 and PS-2 in the cerebral cortex produced by treatment with CRP or Aβ25-35. Immunoblotting analysis showed that while expression of APP was increased in both the cerebral cortex and the hippocampus, expression of IL-1β, BACE, and TNF-α was increased only in the hippocampus. The results suggest that CRP contributes to memory loss and early phase of pathogenesis of AD. CRP can be a novel target for therapeutic intervention of AD.
- Subjects
MEMORY research; MEMORY disorders; LABORATORY rats; HIPPOCAMPUS (Brain); LIMBIC system; ALZHEIMER'S disease; NEUROCHEMISTRY; C-reactive protein; ALPHA macroglobulins
- Publication
Psychopharmacology, 2009, Vol 204, Issue 4, p705
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-009-1499-2