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

Aug 21, 2015American journal of physiology. Regulatory, integrative and comparative physiology

Lower brain stem neurons involved in activating brain GLP-1 receptors

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Abstract

Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein showed strong innervation of spinal autonomic neurons by brain stem PPG neurons.

GLP-1 affects central autonomic neurons involved in cardiovascular control, thermogenesis, and energy balance.
PPG neurons in the nucleus tractus solitarii and medullary intermediate reticular nucleus project to central autonomic control regions and mesolimbic reward centers.
Electrical recordings indicate that PPG neurons receive synaptic inputs from vagal afferents, which convey signals of satiation.
CCK and leptin increased electrical activity in PPG neurons, suggesting that satiation may drive their activation.
PPG neurons could play a critical role in responding to both immediate and long-term energy and feeding status indicators.

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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.

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

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