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Monocytes, microglia, and CD 200‐ CD 200R1 signaling are essential in the transmission of inflammation from the periphery to the central nervous system
Author(s) -
Xie Xin,
Luo Xiaoguang,
Liu Na,
Li Xiaohong,
Lou Fan,
Zheng Yumin,
Ren Yan
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13972
Subject(s) - microglia , inflammation , substantia nigra , neuroinflammation , tumor necrosis factor alpha , lipopolysaccharide , immunology , central nervous system , chemistry , biology , dopaminergic , endocrinology , dopamine
Peripheral inflammation is known to trigger neuroinflammation and neurodegenerative disease. However, the key components during the propagation of inflammation from the periphery to the central nervous system ( CNS ) remain unclear. Lipopolysaccharide ( LPS ) was administered to Sprague–Dawley rats to induce peripheral inflammation. An intravenous injection and an intranigral injection of clodronate liposomes were given to deplete monocytes and microglia, respectively. Recombinant CD 200 fusion protein ( CD 200Fc) or an anti‐ CD 200R1 antibody was injected into the substantia nigra to manipulate the involvement of CD 200 and CD 200R1. Immunohistochemistry and immunofluorescence staining were used to measure microglial activation and dopaminergic neuronal loss. The expression of brain pro‐inflammatory cytokines (i.e., tumor necrosis factor alpha, IL ‐1β) and CD 200‐ CD 200R1 signaling were measured by quantitative RT ‐ PCR . Our data showed that the peripheral LPS injection activated the microglia and induced an increase in the levels of pro‐inflammatory cytokines (i.e., tumor necrosis factor alpha, IL ‐1β). The depletion of either monocytes or microglia suppressed these inflammatory effects that were induced by peripheral LPS administration. The peripheral LPS injection increased the expression of CD 200 and CD 200R1 in the substantia nigra. Dopaminergic neuronal loss induced by the peripheral LPS injection was accelerated by the blockade of CD 200‐ CD 200R1 signaling with an anti‐ CD 200R1 antibody and attenuated by intensifying the signaling with CD 200Fc. These results highlight the importance of monocytes, microglia, and CD 200‐ CD 200R1 signaling in the transmission of inflammation from the periphery to the CNS .