Characterization of the Glucagonlike Peptide-1 Receptor in Male Mouse Brain Using a Novel Antibody and In Situ Hybridization

Abstract Glucagonlike peptide 1 (GLP-1) is a physiological regulator of appetite, and long-acting GLP-1 receptor (GLP-1R) agonists lower food intake and body weight in both human and animal studies. The effects are mediated through brain GLP-1Rs, and several brain nuclei expressing the GLP-1R may be...

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Published in:Endocrinology (Philadelphia) 2018-02, Vol.159 (2), p.665-675
Main Authors: Jensen, Casper Bo, Pyke, Charles, Rasch, Morten Grønbech, Dahl, Anders Bjorholm, Knudsen, Lotte Bjerre, Secher, Anna
Format: Article
Language:English
Subjects:
Antibodies
Appetite
Body weight
Brain
Brain mapping
Brain stem
Endocrinology
Food intake
Gene expression
Hybridization
Hypothalamus
Image analysis
Image processing
Immunohistochemistry
mRNA
Peptide mapping
Peptides
Proteins
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Summary:Abstract Glucagonlike peptide 1 (GLP-1) is a physiological regulator of appetite, and long-acting GLP-1 receptor (GLP-1R) agonists lower food intake and body weight in both human and animal studies. The effects are mediated through brain GLP-1Rs, and several brain nuclei expressing the GLP-1R may be involved. To date, the mapping of the complete location of GLP-1R protein in the brain has been challenged by lack of good antibodies and the discrepancy between mRNA and protein, especially relevant in neuronal axonal processes. Here, we present a specific monoclonal GLP-1R antibody for immunohistochemistry with murine tissue and show detailed distribution of GLP-1R expression, as well as mapping of GLP-1R mRNA by nonradioactive in situ hybridization. Semiautomated image analysis was performed to map the GLP-1R distribution to atlas plates from the Allen Institute for Brain Science. The GLP-1R was abundantly expressed in numerous regions, including the septal nucleus, hypothalamus, and brain stem. GLP-1R protein expression was also observed on neuronal projections in brain regions devoid of any mRNA that has not been observed in earlier reports. Taken together, these findings provide knowledge on GLP-1R expression in neuronal cell bodies and neuronal projections. A novel glucagonlike peptide 1 receptor (GLP-1R) antibody was used to map expression of GLP-1R in neuronal cell bodies and projections through the mouse brain and compared to GLP-1R mRNA expression.
ISSN:1945-7170
0013-7227
1945-7170
DOI:10.1210/en.2017-00812