Comprehensive Gene Expression Profiling in the Prefrontal Cortex Links Immune Activation and Neutrophil Infiltration to Antinociception
| Autor: | Kay-Wee Poh, Jin-Fei Yeo, Wei-Yi Ong, Christian S. Stohler |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Pathology Prefrontal Cortex Inflammation PTPRC Mice Immune system Internal medicine Gene expression medicine Animals Prefrontal cortex CCL12 biology Gene Expression Profiling General Neuroscience Neural Inhibition Articles Barrel cortex Mice Inbred C57BL Gene expression profiling Chemotaxis Leukocyte Endocrinology Neutrophil Infiltration biology.protein Chronic Pain medicine.symptom |
| Zdroj: | The Journal of Neuroscience. 32:35-45 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Functional neuroimaging studies have implicated the prefrontal cortex (PFCTX) in descending modulation of pain and the placebo effect. This study was performed to elucidate comprehensive PFCTX gene expression in an animal model of persistent trigeminal pain. Adult male C57BL/6J mice received facial carrageenan injection and showed sustained increase in nociceptive responses. Microarray analyses of differentially expressed genes in the PFCTX at 3 d after injection showed “immune system process” as the dominant ontology term and increased mRNA expression ofS100a8,S100a9,Lcn2,Il2rg,Fcgr1,Fcgr2b,C1qb,Ptprc,Ccl12, andCd52were verified by RT-PCR. Upregulation of S100A8, S100A9, and lipocalin 2 (LCN2) were confirmed by Western blots, and cells in the PFCTX were double immunolabeled with MPO, indicating they were neutrophils. Analyses of blood of facial carrageenan-injected mice also showed increased mRNA expression of these markers, suggesting transmigration of activated neutrophils into the brain. Other immune-related genes,Il2rg,Fcgr2b,C1qb,Ptprc, andCcl12were upregulated in the PFCTX but not blood. Approximately 70% of S100A9-positive cells in the PFCTX of carrageenan-injected mice were located in capillaries adherent to endothelial cells, whereas 30% were within the brain parenchyma. Carrageenan-injected mice showed significantly reduced nociceptive responses after injection of C terminus of murine S100A9 protein in the lateral ventricles and PFCTX but not somatosensory barrel cortex. Together, these findings demonstrate activation of immune-related genes in the PFCTX during inflammatory pain and highlight an exciting role of neutrophils in linking peripheral inflammation with immune activation of the PFCTX and antinociception. |
| Databáze: | OpenAIRE |
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