PMID- 21029241
OWN - NLM
STAT- MEDLINE
DCOM- 20110818
LR  - 20211020
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 21
IP  - 3
DP  - 2011 May
TI  - Neuronal MCP-1 mediates microglia recruitment and neurodegeneration induced by 
      the mild impairment of oxidative metabolism.
PG  - 279-97
LID - 10.1111/j.1750-3639.2010.00445.x [doi]
AB  - 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 
      knockout 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 by 
      microglia recruitment/activation, which exacerbated neurodegeneration.
CI  - (c) 2010 The Authors; Brain Pathology (c) 2010 International Society of 
      Neuropathology.
FAU - Yang, Guang
AU  - Yang G
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 
      Graduate School of the Chinese Academy of Sciences, Shanghai, China.
FAU - Meng, Ya
AU  - Meng Y
FAU - Li, Wenxia
AU  - Li W
FAU - Yong, Yue
AU  - Yong Y
FAU - Fan, Zhiqin
AU  - Fan Z
FAU - Ding, Hanqing
AU  - Ding H
FAU - Wei, Youzhen
AU  - Wei Y
FAU - Luo, Jia
AU  - Luo J
FAU - Ke, Zun-Ji
AU  - Ke ZJ
LA  - eng
GR  - R01 AA017226-01/AA/NIAAA NIH HHS/United States
GR  - AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA015407-01A1/AA/NIAAA NIH HHS/United States
GR  - R01 AA015407-06/AA/NIAAA NIH HHS/United States
GR  - R01 AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA017226/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101103
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Animals
MH  - Cell Death/physiology
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokines/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/immunology/*physiology
MH  - Nerve Degeneration/*metabolism/pathology
MH  - Neurons/*metabolism/pathology
MH  - Oxidation-Reduction
MH  - Posterior Thalamic Nuclei/cytology/*metabolism/pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Thiamine Deficiency/immunology/*metabolism
PMC - PMC3046243
MID - NIHMS241556
EDAT- 2010/10/30 06:00
MHDA- 2011/08/19 06:00
PMCR- 2010/11/03
CRDT- 2010/10/30 06:00
PHST- 2010/10/30 06:00 [entrez]
PHST- 2010/10/30 06:00 [pubmed]
PHST- 2011/08/19 06:00 [medline]
PHST- 2010/11/03 00:00 [pmc-release]
AID - BPA445 [pii]
AID - 10.1111/j.1750-3639.2010.00445.x [doi]
PST - ppublish
SO  - Brain Pathol. 2011 May;21(3):279-97. doi: 10.1111/j.1750-3639.2010.00445.x. Epub 
      2010 Nov 3.