Excitotoxic brain injury stimulates expression of the chemokine receptor CCR5 in neonatal rats.
Chemokines interact with specific G-protein-coupled receptors to activate and direct recruitment of immune cells. Some chemokines are up-regulated in pathological conditions of the central nervous system, and recently several chemokine receptors, including CCR5, were identified in the brain. However, little is known about the regulation of expression of chemokine receptors in the brain. Direct intracerebral injection of N-methyl-D-aspartate (NMDA), an excitatory amino acid agonist, elicits reproducible focal excitotoxic brain injury; in neonatal rats, intrahippocampal NMDA injection stimulates expression of pro-inflammatory cytokines and elicits a robust microglia/monocyte response. We hypothesized that NMDA-induced neurotoxicity would also stimulate expression of CCR5 in the neonatal rat brain. We evaluated the impact of intrahippocampal injections of NMDA on CCR5 expression in postnatal day 7 rats. Reverse transcription polymerase chain reaction revealed an increase in hippocampal CCR5 mRNA expression 24 hours after lesioning, and in situ hybridization analysis demonstrated that CCR5 mRNA was expressed in the lesioned hippocampus and adjacent regions. Western blot analysis demonstrated increased CCR5 protein in hippocampal tissue extracts 32 hours after lesioning. Complementary immunocytochemistry studies identified both infiltrating microglia/monocytes and injured neurons as the principal CCR5-immunoreactive cells. These results provide the first evidence that acute excitotoxic injury regulates CCR5 expression in the developing rat brain.
Galasso
J M
JM
Neuroscience Program, University of Michigan, Ann Arbor 48109-0646, USA.
Harrison
J K
JK
Silverstein
F S
FS
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000633:toxicity; D015497:HIV-1; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016202:N-Methylaspartate / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019713:Receptors, CCR5 / Q000096:biosynthesis*
D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D019713:Receptors, CCR5; D016202:N-Methylaspartate