PMID- 12106688
OWN - NLM
STAT- MEDLINE
DCOM- 20021106
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 103
IP  - 1-2
DP  - 2002 Jun 30
TI  - Ablation of the chemokine monocyte chemoattractant protein-1 delays retrograde 
      neuronal degeneration, attenuates microglial activation, and alters expression of 
      cell death molecules.
PG  - 12-27
AB  - The mechanisms regulating retrograde neuronal degeneration and subsequent death 
      of thalamic neurons following cortical injury are not well understood. However, 
      the delay in the onset of retrograde cell death and observed morphological 
      changes are consistent with apoptosis. Our previous studies demonstrated that 
      monocyte chemoattractant protein-1 (MCP-1), a beta-chemokine that attracts cells 
      of monocytic origin to sites of injury, is rapidly and specifically expressed in 
      the lateral geniculate nucleus following visual cortical lesions. To determine 
      the potential role of MCP-1 in retrograde degeneration, the present study 
      examined the effect of genetic deletion of MCP-1 (MCP-1 KO or -/-) or its high 
      affinity receptor CCR2 (CCR2 KO or -/-) on thalamic microglial activation and 
      neuronal cell death following aspiration lesions of the visual cortex in adult 
      mice. Deletion of the MCP-1 gene delayed microglial activation and transiently 
      improved the survival of thalamic neurons. Deletion of the CCR2 receptor resulted 
      in a significant increase in apoptosis as measured by nucleosomal fragmentation 
      after injury compared to wild-type mice, but did not alter neuron survival, 
      suggesting that glial apoptosis is increased in the receptor knockout mice. 
      Investigation of Bcl-2, Bax, Fas, Fas ligand (FasL) and activated caspase-3, key 
      regulators of apoptosis that can be modulated by cytokines, revealed complex 
      alterations of mRNA and protein levels in MCP-1(-/-) and CCR2(-/-) mice. As 
      examples, Bcl-2 protein was detected in wild-type, but not in MCP-1(-/-) mice. 
      Caspase-3 activity was higher in MCP-1(-/-) mice compared to wild-type and 
      CCR2(-/-) mice at 5 days after injury. High levels of activated caspase-3 
      correlate with the beginning of a period of delayed, but rapid cell death in the 
      thalami of MCP-1(-/-) mice. In summary, our data strongly suggest that MCP-1 is 
      involved in early microglial response to axotomy and that modulation of this 
      chemokine could provide a novel strategy for improved neuronal survival following 
      injury to the central nervous system.
CI  - Copyright 2002 Elsevier Science B.V.
FAU - Muessel, Michelle J
AU  - Muessel MJ
AD  - Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 
      Rainbow Blvd., Kansas City, KS 66160-7400, USA.
FAU - Klein, Robert M
AU  - Klein RM
FAU - Wilson, Angela M
AU  - Wilson AM
FAU - Berman, Nancy E J
AU  - Berman NE
LA  - eng
GR  - HD02528/HD/NICHD NIH HHS/United States
GR  - NS38282/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Bax protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (fas Receptor)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Survival/genetics/physiology
MH  - Chemokine CCL2/*genetics
MH  - Female
MH  - Gene Expression/genetics/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/*pathology/physiology
MH  - Microsomes/physiology
MH  - Nerve Degeneration/pathology/*physiopathology
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-bcl-2/genetics
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics
MH  - Thalamus/*pathology
MH  - Up-Regulation/genetics/physiology
MH  - bcl-2-Associated X Protein
MH  - fas Receptor/genetics
EDAT- 2002/07/11 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/07/11 10:00
PHST- 2002/07/11 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/07/11 10:00 [entrez]
AID - S0169328X02001584 [pii]
AID - 10.1016/s0169-328x(02)00158-4 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2002 Jun 30;103(1-2):12-27. doi: 
      10.1016/s0169-328x(02)00158-4.