PMID- 15886005
OWN - NLM
STAT- MEDLINE
DCOM- 20060123
LR  - 20070813
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 20
IP  - 2
DP  - 2005 Nov
TI  - MCP-1 and murine prion disease: separation of early behavioural dysfunction from 
      overt clinical disease.
PG  - 283-95
AB  - Prion diseases are chronic, fatal neurodegenerative conditions of the CNS. We 
      have investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the 
      ME7 model of murine prion disease. MCP-1 expression increased in the CNS 
      throughout disease progression and was positively correlated with microglial 
      activation. We subsequently compared the inflammatory response, pathology and 
      behavioural changes in wild-type (wt) mice and MCP-1 knockout mice (MCP-1-/-) 
      inoculated with ME7. Late-stage clinical signs were delayed by 4 weeks in 
      MCP-1-/- mice, and survival time increased by 2-3 weeks. By contrast, early 
      changes in affective behaviours and locomotor activity were not delayed in onset. 
      There was also no difference in microglial activation or neuronal death in the 
      hippocampus and thalamus of wt mice and MCP-1-/- mice. These results highlight an 
      important dissociation between prolonged survival, early behavioural dysfunction 
      and hippocampal/thalamic pathology when considering therapeutic intervention for 
      human prion diseases and other chronic neurodegenerative conditions.
FAU - Felton, L M
AU  - Felton LM
AD  - CNS Inflammation Group, School of Biological Sciences, University of Southampton, 
      Southampton, SO16 7PX, UK. lmf1@soton.ac.uk
FAU - Cunningham, C
AU  - Cunningham C
FAU - Rankine, E L
AU  - Rankine EL
FAU - Waters, S
AU  - Waters S
FAU - Boche, D
AU  - Boche D
FAU - Perry, V H
AU  - Perry VH
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (PrPSc Proteins)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Cell Death/genetics
MH  - Chemokine CCL2/*genetics
MH  - Disease Models, Animal
MH  - Encephalitis/genetics/*metabolism/physiopathology
MH  - Female
MH  - Gliosis/genetics/*metabolism/physiopathology
MH  - Hippocampus/metabolism/pathology/physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/*metabolism
MH  - Nerve Degeneration/genetics/*metabolism/physiopathology
MH  - PrPSc Proteins/toxicity
MH  - Prion Diseases/genetics/*metabolism/physiopathology
MH  - Survival Rate
MH  - Thalamus/metabolism/pathology/physiopathology
EDAT- 2005/05/12 09:00
MHDA- 2006/01/24 09:00
CRDT- 2005/05/12 09:00
PHST- 2005/01/27 00:00 [received]
PHST- 2005/03/08 00:00 [revised]
PHST- 2005/03/13 00:00 [accepted]
PHST- 2005/05/12 09:00 [pubmed]
PHST- 2006/01/24 09:00 [medline]
PHST- 2005/05/12 09:00 [entrez]
AID - S0969-9961(05)00084-7 [pii]
AID - 10.1016/j.nbd.2005.03.008 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2005 Nov;20(2):283-95. doi: 10.1016/j.nbd.2005.03.008.