Neuronal MCP-1 Mediates Microglia Recruitment and Neurodegeneration Induced by the Mild Impairment of Oxidative Metabolism

Guang Yang; Ya Meng; Wenxia Li; Yue Yong; Zhiqin Fan; Hanqing Ding; Youzhen Wei; Jia Luo; Zun-Ji Ke

doi:10.1111/j.1750-3639.2010.00445.x

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Neuronal MCP-1 Mediates Microglia Recruitment and Neurodegeneration Induced by the Mild Impairment of Oxidative Metabolism

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Neuronal MCP-1 Mediates Microglia Recruitment and Neurodegeneration Induced by the Mild Impairment of Oxidative Metabolism

Guang Yang, Ya Meng, Wenxia Li, Yue Yong, Zhiqin Fan, Hanqing Ding, Youzhen Wei, Jia Luo and Zun-Ji Ke

Brain pathology (Zurich, Switzerland), Vol.21(3), pp.279-297

05/2011

DOI: 10.1111/j.1750-3639.2010.00445.x

PMCID: PMC3046243

PMID: 21029241

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Abstract

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), which are common features of neurodegenerative diseases. We evaluated the role of chemokines in neurodegeneration and the underlying mechanism in a TD model. Among the chemokines examined, TD selectively induced neuronal expression of monocyte chemoattractant protein-1 (MCP-1) in the SmTN prior to microglia activation and neurodegeneration. The conditioned medium collected from TD-induced neurons caused microglia activation. With a neuron/microglia co-culture system, we showed that MCP-1-induced neurotoxicity required the presence of microglia and exogenous MCP-1 was able to activate microglia and stimulated microglia to produce cytokines. 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 mild impairment of oxidative metabolism caused microglia recruitment/activation, which exacerbated neurodegeneration.

chemokines

microglia activation

neurodegeneration

oxidative stress

Thiamine deficiency

Details

Title: Subtitle: Neuronal MCP-1 Mediates Microglia Recruitment and Neurodegeneration Induced by the Mild Impairment of Oxidative Metabolism
Creators: Guang Yang - Chinese Academy of Sciences
Ya Meng - Chinese Academy of Sciences
Wenxia Li - Chinese Academy of Sciences
Yue Yong - Chinese Academy of Sciences
Zhiqin Fan - Chinese Academy of Sciences
Hanqing Ding - Chinese Academy of Sciences
Youzhen Wei - Chinese Academy of Sciences
Jia Luo - University of Kentucky
Zun-Ji Ke - Shanghai Institutes for Biological Sciences
Resource Type: Journal article
Publication Details: Brain pathology (Zurich, Switzerland), Vol.21(3), pp.279-297
DOI: 10.1111/j.1750-3639.2010.00445.x
PMID: 21029241
PMCID: PMC3046243
NLM abbreviation: Brain Pathol
ISSN: 1015-6305
eISSN: 1750-3639
Language: English
Date published: 05/2011
Academic Unit: Pathology
Record Identifier: 9984201258802771

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