A novel mouse model of glucagon‐like peptide‐1 receptor expression: A look at the brain

• Published in: Journal of comparative neurology (1911) Vol. 528; no. 14; pp. 2445 - 2470
• Main Authors: Graham, Devon L., Durai, Heather H., Trammell, Taylor S., Noble, Brenda L., Mortlock, Douglas P., Galli, Aurelio, Stanwood, Gregg D.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.10.2020; Wiley Subscription Services, Inc
• Subjects: Amygdala; Animals; Artificial chromosomes; Bacterial artificial chromosomes; Brain - metabolism; Calbindin; Central nervous system; Cerebral cortex; Energy balance; Food intake; Gastric emptying; GLP‐1; GLP‐1R; Glucagon; Glucagon-Like Peptide 1 - metabolism; Glutamatergic transmission; Hedonic response; Hippocampus; Homeostasis; Hybridization; hypothalamus; Hypothalamus (lateral); Immunohistochemistry; incretin; Insulin secretion; lateral septum; Mice; Mice, Transgenic; Models, Animal; Motivation; Neostriatum; Neurons; Neurons - metabolism; Peptides; Periaqueductal gray area; RRID:AB_10000320; RRID:AB_10000347; RRID:AB_10013483; RRID:AB_10617228; RRID:AB_11211549; RRID:AB_11212597; RRID:AB_2079751; RRID:AB_2088494; RRID:AB_2255365; RRID:AB_2278725; RRID:AB_2298772; RRID:AB_2534023; RRID:AB_2811192; RRID:AB_477329; RRID:AB_477560; Satiety; Septum; striatum; Transcription; Transcriptome; transgenic; Transgenic mice; γ-Aminobutyric acid; GLP-1; RRID:AB_2255365; RRID:AB_10000320; RRID:AB_2298772; RRID:AB_11212597; incretin; RRID:AB_2088494; RRID:AB_477329; lateral septum; RRID:AB_2278725; RRID:AB_10013483; RRID:AB_477560; RRID:AB_10617228; striatum; RRID:AB_2534023; transgenic; RRID:AB_10000347; RRID:AB_11211549; hypothalamus; GLP-1R; RRID:AB_2079751; RRID:AB_2811192
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24905

Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone with a number of functions to maintain energy homeostasis and contribute to motivated behavior, both peripherally and within the central nervous system (CNS). These functions, which include insulin secretion, gastric emptying, satiety, and the hedonic aspects of food and drug intake, are primarily mediated through stimulation of the GLP‐1 receptor. While this receptor plays an important role in a variety of physiological outcomes, data regarding its CNS expression has been primarily limited to regional receptor binding and single‐label transcript expression studies. We thus developed a bacterial artificial chromosome transgenic mouse, in which expression of a red fluorescent protein (mApple) is driven by the GLP‐1R promoter. Using this reporter mouse, we characterized the regional and cellular expression patterns of GLP‐1R expressing cells in the CNS, using double‐label immunohistochemistry and in situ hybridization. GLP‐1R‐expressing cells were enriched in several key brain regions and circuits, including the lateral septum, hypothalamus, amygdala, bed nucleus of the stria terminalis, hippocampus, ventral midbrain, periaqueductal gray, and cerebral cortex. In most regions, GLP‐1R primarily colocalized with GABAergic neurons, except within some regions such as the hippocampus, where it was co‐expressed in glutamatergic neurons. GLP‐1R‐mApple cells were highly co‐expressed with 5‐HT3 receptor‐containing neurons within the cortex and striatum, as well as with dopamine receptor‐ and calbindin‐expressing cells within the lateral septum, the brain region in which GLP‐1R is most highly expressed. In this manuscript, we provide detailed images of GLP‐1R‐mApple expression and distribution within the brain and characterization of these neurons. We developed a BAC transgenic mouse model of the glucagon‐like peptide‐1 receptor (GLP‐1R) whereby expression of a red fluorescent protein (mApple) was driven by the GLP‐1R promoter. We further characterized the expression patterns and cellular specificity of these neurons in order to better understand the functional roles of GLP‐1R.