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Quantifying the Heterogeneous Distribution of a Synaptic Protein in the Mouse Brain Using Immunofluorescence
Published on: January 29, 2019
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.
Abstract:
Previous studies in rats have demonstrated that microsomal prostaglandin E synthase-1 (mPGES-1) is induced in brain vascular cells that also express inducible cyclooxygenase-2, suggesting that such cells are the source of the increased PGE2 levels that are seen in the brain following peripheral immune stimulation, and that are associated with sickness responses such as fever, anorexia, and stress hormone release. However, while most of what is known about the functional role of mPGES-1 for these centrally evoked symptoms is based on studies on genetically modified mice, the cellular localization of mPGES-1 in the mouse brain has not been thoroughly determined. Here, using a newly developed antibody that specifically recognizes mouse mPGES-1 and dual-labeling for cell-specific markers, we report that mPGES-1 is constitutively expressed in the mouse brain, being present not only in brain endothelial cells, but also in several other cell types and structures, such as capillary-associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. Regional differences were seen with particularly prominent labeling in autonomic relay structures such as the area postrema, the subfornical organ, the paraventricular hypothalamic nucleus, the arcuate nucleus, and the preoptic area. Following immune stimulation, mPGES-1 in brain endothelial cells, but not in other mPGES-1-positive cells, was coexpressed with cyclooxygenase-2, whereas there was no coexpression between mPGES-1 and cyclooxygenase-1. These data imply a widespread synthesis of PGE2 or other mPGES-1-dependent products in the mouse brain that may be related to inflammation-induced sickness symptom as well as other functions, such as blood flow regulation.
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.

