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Neuronal MCP‐1 Mediates Microglia Recruitment and Neurodegeneration Induced by Thiamine Deficiency
Author(s) -
Yang Guang,
Ke Zunji
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.627.3
Subject(s) - neurodegeneration , microglia , neuroinflammation , neurotoxicity , neuroscience , biology , chemistry , microbiology and biotechnology , inflammation , immunology , medicine , disease , organic chemistry , toxicity
Chemokines are implicated in the neuroinflammation of several chronic neurodegenerative disorders. However, the precise role of chemokines in neurodegeneration is unknown. Thiamine deficiency (TD) causes abnormal oxidative metabolism in the brain as well as a well‐defined microglia activation and neurodegeneration in the submedial thalamus nucleus (SmTN). We evaluated the role of chemokines in neurodegeneration and the underlying mechanism in a TD model. TD selectively induced neuronal expression of monocyte chemoattractant protein‐1 (MCP‐1) in the SmTN prior to microglia activation and neurodegeneration. we showed that MCP‐1‐induced neurotoxicity required the presence of microglia. A MCP‐1 neutralizing antibody inhibited MCP‐1‐induced microglia activation and neuronal death in culture and in the thalamus. MCP‐1 knock‐out mice were resistant to TD‐induced neuronal death in SmTN. TD selectively induced the accumulation of reactive oxygen species in neurons, and antioxidants blocked TD‐induced MCP‐1 expression. Together, our results indicated an induction of neuronal MCP‐1 during TD caused microglia recruitment/activation, which exacerbated neurodegeneration.