Dataset Information

Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain.

ABSTRACT: 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.

SUBMITTER: Heppner KM

PROVIDER: S-EPMC4272390 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain.

Heppner Kristy M KM Kirigiti Melissa M Secher Anna A Paulsen Sarah Juel SJ Buckingham Rikley R Pyke Charles C Knudsen Lotte B LB Vrang Niels N Grove Kevin L KL

Endocrinology 20150101 1

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 ma ...[more]

PMID: 25380238

Similar Datasets

Project description:Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1-4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys' motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets for intervention to improve social outcomes in at-risk young monkeys.

Project description:An array of 13 biochemically well defined molecular forms of bovine, human and newly cloned rhesus macaque (Macaca mulatta) AChEs (acetylcholinesterases) differing in glycosylation and subunit assembly status were subjected to comparative pharmacokinetic studies in mice and rhesus macaques. The circulatory lifetimes of recombinant bovine, macaque and human AChEs in mice were governed by previously determined hierarchical rules; the longest circulatory residence time was obtained when AChE was fully sialylated and tetramerized [Kronman, Chitlaru, Elhanany, Velan and Shafferman (2000) J. Biol. Chem. 275, 29488-29502; Chitlaru, Kronman, Velan and Shafferman (2001) Biochem. J. 354, 613-625]. In rhesus macaques, bovine molecular forms still obeyed the same hierarchical rules, whereas primate AChEs showed significant deviation from this behaviour. Residence times of human and rhesus AChEs were effectively extended by extensive sialylation, but subunit tetramerization and N-glycan addition had a marginal effect on their circulatory longevity in macaques. It appears that the major factor responsible for the differential pharmacokinetics of bovine and primate AChEs in macaques is related to differences in primary structure, suggesting the existence of a specific mechanism for the circulatory clearance of primate AChEs in rhesus macaques. The 35 amino acids that differ between bovine and primate AChEs are clustered within three defined domains, all located at the enzyme surface, and may therefore mediate the facilitated removal of primate cholinesterases specifically from the circulation of monkeys. These surface domains can be effectively masked by poly(ethylene glycol) appendage, resulting in the generation of chemically modified human and macaque AChEs that reside in the circulation for extraordinarily long periods of time (mean residence time of 10000 min). This extended residence time is similar to that displayed by native macaque butyrylcholinesterase (9950 min), which is the prevalent cholinesterase form in the circulation of adult macaques.

Dataset Information

Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain.

Publications

Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets