Chemerin-9 Peptide Enhances Memory and Ameliorates Aβ1–42-Induced Object Memory Impairment in Mice
| Autor: | YaQin Lu, ZhenXiu Jiang, Qin Yu, Zelin Lei, Xue Bai |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology medicine.medical_specialty biology Chemistry Pharmaceutical Science Hippocampus Inflammation General Medicine CMKLR1 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology 030220 oncology & carcinogenesis Internal medicine biology.protein medicine Chemerin Memory impairment Tumor necrosis factor alpha medicine.symptom Receptor Neuroinflammation |
| Zdroj: | Biological and Pharmaceutical Bulletin. 43:272-283 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b19-00510 |
| Popis: | 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 β1-42 (Aβ1-42) 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 Aβ1-42 share the same receptor. Thus, we hypothesized that chemerin (C9), a chemerin-derived nonapeptide, may have the potential to ameliorate Aβ1-42 mediated AD disease progression. The results showed that an intracerebroventricular (i.c.v.) injection of C9 (8 µg/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 µg/kg) was infused into the hippocampus. Moreover, we found that treatment with C9 reversed the deficits in memory and learning ability induced by oligomeric Aβ1-42. Meanwhile, C9 also significantly inhibited Aβ1-42-induced increases in the levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) 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 Aβ1-42-induced memory impairment, suggesting that C9 may potentially represent a novel strategy for the treatment of AD. |
| Databáze: | OpenAIRE |
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