TY - JOUR
T1 - Expression and distribution of glucagon-like peptide-1 receptor mrna, protein and binding in the male nonhuman primate (macaca mulatta) brain
AU - Heppner, Kristy M.
AU - Kirigiti, Melissa
AU - Secher, Anna
AU - Paulsen, Sarah Juel
AU - Buckingham, Rikley
AU - Pyke, Charles
AU - Knudsen, Lotte B.
AU - Vrang, Niels
AU - Grove, Kevin L.
N1 - Publisher Copyright:
© 2015 by the Endocrine Society Received April 18, 2014.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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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U2 - 10.1210/en.2014-1675
DO - 10.1210/en.2014-1675
M3 - Article
C2 - 25380238
AN - SCOPUS:84919725884
SN - 0013-7227
VL - 156
SP - 255
EP - 267
JO - Endocrinology
JF - Endocrinology
IS - 1
ER -