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

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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 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.

Results

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.

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.

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Acknowledgment

This work was supported by a research grant from the Guangdong Natural Science Foundation (No. 7117782). The authors do not have any financial relationship with this organization.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Huan-Bing Lin, Xue-Mei Yang, Yu-Fang Cheng, Han-Ting Zhang & Jiang-Ping Xu

  2. Department of Pharmacology, School of Pharmacy, The Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Tie-Jun Li

  3. Department of Behavioral Medicine and Psychiatry, West Virginia University Health Sciences Center, Morgantown, WV, 26506, USA

    Han-Ting Zhang

  4. Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, WV, 26506, USA

    Han-Ting Zhang

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  1. Huan-Bing Lin
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  3. Tie-Jun Li
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  4. Yu-Fang Cheng
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Correspondence to Tie-Jun Li or Jiang-Ping Xu.

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Tie-Jun Li and Jiang-Ping Xu equally contributed to this work.

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Lin, HB., Yang, XM., Li, TJ. et al. Memory deficits and neurochemical changes induced by C-reactive protein in rats: implication in Alzheimer’s disease. Psychopharmacology 204, 705–714 (2009). https://doi.org/10.1007/s00213-009-1499-2

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  • DOI: https://doi.org/10.1007/s00213-009-1499-2

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