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PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation

Trapp, S; Cork, SC; (2015) PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology , 309 (8) R795-R804. 10.1152/ajpregu.00333.2015. Green open access

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Abstract

Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation.

Type: Article
Title: PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajpregu.00333.2015
Publisher version: http://dx.doi.org/10.1152/ajpregu.00333.2015
Language: English
Additional information: Copyright © 2015 the American Physiological Society
Keywords: appetite, brain stem, glucagon-like peptide-1, hippocampus, neuroanatomy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1471118
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