Memory deficits and neurochemical changes induced by C-reactive protein in rats: implication in Alzheimer's disease.
BACKGROUND
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.
Lin
Huan-Bing
HB
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Yang
Xue-Mei
XM
Li
Tie-Jun
TJ
Cheng
Yu-Fang
YF
Zhang
Han-Ting
HT
Xu
Jiang-Ping
JP
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000008:administration & dosage / Q000378:metabolism*; D002540:Cerebral Cortex / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000008:administration & dosage; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018836:Inflammation Mediators; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D012313:RNA; D002097:C-Reactive Protein