期刊
JOURNAL OF NEUROTRAUMA
卷 36, 期 6, 页码 903-918出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2018.5783
关键词
adiponectin; chemotaxis; myelin-laden macrophage; myelin lipid accumulation; neuroinflammation; spinal cord injury
资金
- National Natural Science Foundation of China [81601065, 31571408, 81501171, 81571395]
- Guangdong Natural Science Foundation [2016A030313105]
- Fundamental Research Funds for the Central Universities [21616339, 17817014]
- Program of Introducing Talents of Discipline to Universities [B14036]
- National Key Research and Development Program of China [2016YFC1306702]
- New Jersey Commission on Spinal Cord Research [CSCR-13IRG006]
Myelin-laden macrophages (mye-M phi), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. We found that in vitro activation of adiponectin receptors (AdipoRs) by their agonist AdipoRon suppressed myelin lipid accumulation in mye-M phi through APPL1/PPAR/LXR/ABCA1-mediated lipid efflux, subsequently inhibiting inflammation and restoring normal function to mye-M phi. In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-M phi-mediated neuroinflammation in neurological disorders involving demyelination.
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