CCR3, CCR2A and macrophage inflammatory protein (MIP)-1a, monocyte chemotactic protein-1 (MCP-1) in the mouse hippocampus during and after pilocarpine-induced status epilepticus (PISE) .
OBJECTIVE
To investigate protein and gene expressions of chemokine subtypes CCR3, CCR2A and their respective ligands macrophage inflammatory protein 1-alpha (MIP-1alpha), monocyte chemotactic protein-1 (MCP-1) in the normal mouse central nervous system (CNS) and in the hippocampus at different time points during and after pilocarpine-induced status epilepticus (PISE).


METHODS
CCR3 and MIP-1alpha protein expressions were mapped in the mouse CNS. The protein and gene expressions of CCR3 and CCR2A and their respective ligands MIP-1alpha, MCP-1 in the hippocampus were studies by immunocytochemical and quantitative real-time RT-PCR during and after PISE.


RESULTS
CCR3 and MIP-1alpha gene expression and immunopositive neurones were broadly distributed in the CNS. CCR3 and CCA2A gene and their protein expression were downregulated in the hippocampus at 1 h during PISE. The protein expression of MIP-1alpha, MCP-1 decreased but gene expression increased at 2 h during PISE. In the hilus of the dentate gyrus, significant reduction of the numbers of CCR3, CCR2A, MCP-1 immunopositive neurones occurred from 1 h during to 2 months after PISE, but the number of MIP-1alpha neurones reduced from 2 h during to 2 months after PISE. Induced expression of CCR3 at 1 week, CCR2A, MCP-1 or MIP-1alpha at 1 week and 2 months after PISE was found in reactive astrocytes. MCP-1 was also demonstrated in the blood vessels of the hippocampus at 2 months after PISE.


CONCLUSIONS
CCR3 and MIP-1alpha may play important functional roles in the mouse brain. The downregulation of CCR3, CCR2A, MIP-1alpha and MCP-1 in the hippocampal neurones at the acute stage during and after PISE may weaken the neuroprotective mechanisms. However, induced expression of MCP-1 in hippocampal blood vessel may be related to changes in permeability of the blood-brain barrier during epileptogenesis.
Xu
J H
JH
Epilepsy Research Lab, National Neuroscience Institute, Singapore.
Long
L
L
Tang
Y C
YC
Zhang
J T
JT
Hut
H T
HT
Tang
F R
FR
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D054405:Chemokine CCL3 / Q000096:biosynthesis*; D003292:Convulsants / Q000494:pharmacology; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D010862:Pilocarpine / Q000494:pharmacology; D054390:Receptors, CCR2 / Q000096:biosynthesis*; D054397:Receptors, CCR3 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*
C491768:Ccl2 protein, mouse; C515351:Ccr3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D003292:Convulsants; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D010862:Pilocarpine