Distribution of microsomal prostaglandin E synthase-1 in the mouse brain

Anna Eskilsson1, Masanori Tachikawa, Ken-Ichi Hosoya

  • 1Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

Insights

Microsomal prostaglandin E synthase-1 (mPGES-1) is widely present in the mouse brain, including endothelial cells and other cell types. Immune stimulation specifically increases mPGES-1 in brain endothelial cells, suggesting its role in sickness responses.

Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • Microsomal prostaglandin E synthase-1 (mPGES-1) induction in rat brain vascular cells correlates with sickness behaviors after immune stimulation.
  • The precise cellular localization of mPGES-1 in the mouse brain has not been fully elucidated, hindering a complete understanding of its function.
  • Previous functional studies relied heavily on genetically modified mice, emphasizing the need for detailed localization data.

Purpose of the Study:

  • To determine the cellular localization of mPGES-1 in the mouse brain using a novel, specific antibody.
  • To investigate the changes in mPGES-1 expression in response to peripheral immune stimulation.
  • To clarify the cell-specific coexpression patterns of mPGES-1 with cyclooxygenase enzymes (COX-1 and COX-2).

Main Methods:

  • Utilized a newly developed antibody for specific detection of mouse mPGES-1.
  • Employed dual-labeling techniques with cell-specific markers for detailed cellular and subcellular localization.
  • Examined mPGES-1 expression in both naive and peripherally immune-stimulated mouse brains.

Main Results:

  • mPGES-1 exhibits constitutive expression in various mouse brain cells, including endothelial cells, pericytes, astroglial cells, leptomeninges, and choroid plexus.
  • Prominent mPGES-1 labeling was observed in autonomic relay structures like the area postrema, subfornical organ, paraventricular nucleus, arcuate nucleus, and preoptic area.
  • Upon immune stimulation, mPGES-1 coexpressed with cyclooxygenase-2 (COX-2) specifically in brain endothelial cells, but not with cyclooxygenase-1 (COX-1) or in other mPGES-1-positive cells.

Conclusions:

  • mPGES-1 is broadly distributed throughout the mouse brain, suggesting widespread synthesis of prostaglandin E2 (PGE2) or related products.
  • The cell-specific induction of mPGES-1 with COX-2 in endothelial cells during immune stimulation implicates these cells in central inflammatory responses.
  • These findings suggest mPGES-1's involvement in inflammation-induced sickness symptoms and other physiological functions, potentially including blood flow regulation.

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