Cognitive, Behavioral, and Systems NeuroscienceResearch PaperPreproglucagon neurons project widely to autonomic control areas in the mouse brain
Highlights
▶Central GLP-1 neurons project to feeding and non-feeding autonomic control regions. ▶Brainstem GLP-1 neurons have axons and dendrites in the area postrema. ▶Genetically altered animals expressing marker proteins are ideal to study anatomy.
Section snippets
Experimental procedures
These studies were performed on nine adult male and eight adult female mGLU-124 Venus YFP mice (Reimann et al., 2008). These will be referred to as YFP-PPG mice in this study. Mice weighed between 25 and 35 g and were 12–16 weeks of age. Males were consistently heavier than females of the same age. All animals were bred in-house, were kept on a 12 h light:dark cycle and had access to food and water ad libitum. All experiments were carried out in accordance with the UK Animals (Scientific
Results
YFP-immunoreactive innervation was assessed in nine adult male and eight adult female YFP-PPG mice. After both immunoperoxidase and immunofluorescent staining, YFP-immunoreactivity was intense throughout the entire cytoplasm of medullary YFP-PPG neurons and it was easy to distinguish between YFP-immunoreactive axons and YFP-immunoreactive dendrites. Varicose YFP-immunoreactive axons had clearly delineated, heavily immunoreactive varicosities and fine intervaricose segments that were constant in
Discussion
We have performed an immunohistochemical study to determine the distribution of brain GLP-1 neurons and their projections between the spinomedullary junction and the anterior wall of the third ventricle in YFP-PPG mice (Reimann et al., 2008). These mice express YFP specifically and exclusively in cells in which the PPG promoter is active (Reimann et al., 2008, Hisadome et al., 2010), that is cells that produce PPG, the precursor for glucagon, as well as for GLP-1, GLP-2 and oxyntomodulin (
Conclusion
In conclusion, our results demonstrate that medullary neurons capable of synthesising GLP-1 innervate primarily brain regions involved in autonomic control. Hence, central PPG neurons are in a prime position to modulate sympathetic and parasympathetic outflow through input at a variety of autonomic locations within the CNS.
Acknowledgments
This work was supported by grants from the Medical Research Council (G0600928), UK to ST and the National Health and Medical Research Council of Australia to ILS (Project Grant 480414, Principal Research Fellowship 229921). FMG and FR are supported by Wellcome Trust Senior Research Fellowships (WT088357 and WT084210). Lee Travis provided expert technical assistance.
References (36)
- et al.
The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway
Brain Res
(2005) - et al.
Electron microscopic observation of delta-opioid receptor-1 in the rat area postrema
Peptides
(1997) - et al.
Electron microscopic observation of mu-opioid receptor in the rat area postrema
Peptides
(1999) - et al.
Glucagon-like peptide-1 7-36: a physiological incretin in man
Lancet
(1987) - et al.
Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem
Neuroscience
(1997) - et al.
Glucose sensing in L cells: a primary cell study
Cell Metab
(2008) - et al.
Distribution of glucagon-like peptide-1 immunoreactivity in the hypothalamic paraventricular and supraoptic nuclei
J Chem Neuroanat
(2008) - et al.
Characterization of brainstem preproglucagon projections to the paraventricular and dorsomedial hypothalamic nuclei
Brain Res
(2007) - et al.
Glucagon-like peptide-1 modulates synaptic transmission to identified pancreas-projecting vagal motoneurons
Peptides
(2007) - et al.
Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity
Diabetes
(2008)
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans
J Clin Invest
The mouse brain in stereotaxic coordinates
Distribution of GLP-1 binding sites in the rat brain: evidence that exendin-4 is a ligand of brain GLP-1 binding sites
Eur J Neurosci
Synaptic relations of GABAergic neurons in the area postrema
Acta Anat (Basel)
Observation of the ultrastructure and synaptic relationships of angiotensin II-like immunoreactive neurons in the rat area postrema
Synapse
Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling
Endocrinology
Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation
Endocrinology
Leptin directly depolarizes preproglucagon neurons in the nucleus tractus solitarius: electrical properties of glucagon-like Peptide 1 neurons
Diabetes
Cited by (150)
Sleep is increased by liraglutide, a glucagon-like peptide-1 receptor agonist, in rats
2023, Brain Research BulletinThe regulation of PKA signaling in obesity and in the maintenance of metabolic health
2022, Pharmacology and TherapeuticsGlucagon-like peptide 1 receptor activation: anti-inflammatory effects in the brain
2024, Neural Regeneration Research