Expression and Distribution of Glucagon-Like Peptide-1 Receptor mRNA, Protein and Binding in the Male Nonhuman Primate (Macaca mulatta) Brain

Nov 8, 2014Endocrinology

Glucagon-like Peptide-1 Receptor Levels and Locations in the Male Monkey Brain

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Abstract

The GLP-1 receptor (GLP-1R) is found in a selective distribution throughout the adult macaque brain.

GLP-1 is released in response to food ingestion and acts as a crucial regulator of autonomic and neuroendocrine functions.
The distribution of GLP-1R mRNA and protein was characterized in the adult macaque using various imaging techniques.
Immunohistochemistry revealed that GLP-1R is localized in cell bodies and fiber terminals across the brain.
The highest levels of GLP-1R were observed in hypothalamic and brainstem regions known to regulate feeding.
Key differences in GLP-1R expression were noted, particularly higher expression in the amygdala of primates compared to rodents.

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Glucagon-like peptide-1 (GLP-1) is released from endocrine L-cells lining the gut in response to food ingestion. However, GLP-1 is also produced in the nucleus of the solitary tract, where it acts as an anorectic neurotransmitter and key regulator of many autonomic and neuroendocrine functions. The expression and projections of GLP-1-producing neurons is highly conserved between rodent and primate brain, although a few key differences have been identified. The GLP-1 receptor (GLP-1R) has been mapped in the rodent brain, but no studies have described the distribution of GLP-1Rs in the nonhuman primate central nervous system. Here, we characterized the distribution of GLP-1R mRNA and protein in the adult macaque brain using in situ hybridization, radioligand receptor autoradiography, and immunohistochemistry with a primate specific GLP-1R antibody. Immunohistochemistry demonstrated that the GLP-1R is localized to cell bodies and fiber terminals in a very selective distribution throughout the brain. Consistent with the functional role of the GLP-1R system, we find the highest concentration of GLP-1R-immunoreactivity present in select hypothalamic and brainstem regions that regulate feeding, including the paraventricular and arcuate hypothalamic nuclei, as well as the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus. Together, our data demonstrate that GLP-1R distribution is highly conserved between rodent and primate, although a few key species differences were identified, including the amygdala, where GLP-1R expression is much higher in primate than in rodent.

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Expression and Distribution of Glucagon-Like Peptide-1 Receptor mRNA, Protein and Binding in the Male Nonhuman Primate (Macaca mulatta) Brain

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