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Molecular Medicine

, Volume 20, Issue 1, pp 601–611 | Cite as

Brain Region-Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin-Induced Inflammation

  • Harold A. Silverman
  • Meghan Dancho
  • Angelique Regnier-Golanov
  • Mansoor Nasim
  • Mahendar Ochani
  • Peder S. Olofsson
  • Mohamed Ahmed
  • Edmund J. Miller
  • Sangeeta S. Chavan
  • Eugene Golanov
  • Christine N. Metz
  • Kevin J. Tracey
  • Valentin A. Pavlov
Research Article

Abstract

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune-brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region-specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches.

Notes

Acknowledgments

This work was supported by the following grants from the National Institute of General Medical Sciences, National Institutes of Health: R01GM057226 (to KJ Tracey) and R01GM089807 (to VA Pavlov).

Supplementary material

10020_2014_2001601_MOESM1_ESM.pdf (447 kb)
Supplementary material, approximately 447 KB.

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© The Author(s) 2014

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Authors and Affiliations

  • Harold A. Silverman
    • 1
    • 2
  • Meghan Dancho
    • 1
  • Angelique Regnier-Golanov
    • 3
  • Mansoor Nasim
    • 4
  • Mahendar Ochani
    • 1
  • Peder S. Olofsson
    • 1
  • Mohamed Ahmed
    • 5
    • 6
  • Edmund J. Miller
    • 2
    • 6
  • Sangeeta S. Chavan
    • 1
  • Eugene Golanov
    • 7
  • Christine N. Metz
    • 2
    • 8
  • Kevin J. Tracey
    • 1
    • 2
  • Valentin A. Pavlov
    • 1
    • 2
  1. 1.Laboratory of Biomedical Science, Center for Biomedical ScienceThe Feinstein Institute for Medical ResearchManhassetUSA
  2. 2.Hofstra North Shore-LIJ School of Medicine at Hofstra UniversityHempsteadUSA
  3. 3.Pediatrics-NeurologyBaylor College of MedicineHoustonUSA
  4. 4.Neuropathology-Anatomic PathologyNorth Shore-LIJ Health SystemNew Hyde ParkUSA
  5. 5.Cohen Children’s Medical CenterNorth Shore-LIJ Health SystemNew Hyde ParkUSA
  6. 6.Center for Heart and Lung ResearchThe Feinstein Institute for Medical ResearchManhassetUSA
  7. 7.The Houston Methodist Research InstituteHoustonUSA
  8. 8.Laboratory of Medicinal BiochemistryThe Feinstein Institute for Medical ResearchManhassetUSA

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