Chemerin-9 Peptide Enhances Memory and Ameliorates A beta(1-42)-Induced Object Memory Impairment in Mice

摘要

Accumulating evidence suggests that the inhibition of neuroinflammation is a potential target for therapeutic or preventive strategies for Alzheimer's disease (AD). Chemerin has attracted particular attention for its role in the regulation of inflammation. In addition, amyloid beta(1-42) (A beta(1-42)) can interact with chemokine-like receptor 1 (CMKLR1), the receptor for chemerin, and induce microglial chemotaxis. Meanwhile, CMKLR1 is expressed in the brain, and both chemerin and A beta(1-42) share the same receptor. Thus, we hypothesized that chemerin (C9), a chemerin-derived nonapeptide, may have the potential to ameliorate A beta(1-42) mediated AD disease progression. The results showed that an intracerebroventricular (i.c.v.) injection of C9 (8 mu g/kg) facilitated memory formation and improved memory retention, as evidenced by the results of both the novel object recognition test (NOR) and object location recognition (OLR) tasks. These memory-enhancing effects of C9 were also observed after C9 (2 mu g/kg) was infused into the hippocampus. Moreover, we found that treatment with C9 reversed the de cits in memory and learning ability induced by oligomeric A beta(1-42). Meanwhile, C9 also signi cantly inhibited A beta(1-42)-induced increases in the levels of pro-in ammatory cytokines such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the hippocampus. The same results were obtained for Western blotting and enzyme-linked immunosorbent assay (ELISA) experiments. Finally, we observed that C9 did not affect locomotor activity, suggesting that its improvement of memory is not a false positive induced by hypolocomotion. In conclusion, C9 may facilitate memory formation, prolong memory retention, and ameliorate A beta(1-42)-induced memory impairment, suggesting that C9 may potentially represent a novel strategy for the treatment of AD.