Memory deficits and neurochemical changes induced by C-reactive protein in rats: implication in Alzheimer's disease.

Abstract:

RATIONALE: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. OBJECTIVE:Experiments were carried out to determine whether CRP impaired memory and altered neurochemical measures associated with AD. METHODS:The effects of intra-cerebroventricular administration of CRP or beta-amyloid peptide 25-35 (Abeta(25-35)) on memory performance were evaluated using rat Morris water-maze and step-through passive avoidance tests; the levels of inflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor (TNF-alpha)), endogenous CRP, and markers of the endogenous production of Abeta, including amyloid precursor protein (APP), presenilins (PS-1 and PS-2), and beta-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. RESULTS:Treatment with CRP (25.6 microg/rat) or Abeta(25-35) (10 microg/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-1beta, IL-6, TNF-alpha, 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 Abeta(25-35). Immunoblotting analysis showed that while expression of APP was increased in both the cerebral cortex and the hippocampus, expression of IL-1beta, BACE, and TNF-alpha was increased only in the hippocampus. CONCLUSIONS: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.

journal_title

Psychopharmacology

authors

Lin HB,Yang XM,Li TJ,Cheng YF,Zhang HT,Xu JP

doi

10.1007/s00213-009-1499-2

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

705-14

issue

4

eissn

0033-3158

issn

1432-2072

journal_volume

204

pub_type

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