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GLP-1 action in the mouse bed nucleus of the stria terminalis
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Williams, Diana L., Lilly, Nicole A., Edwards, Ian, Yao, Pallas, Richards, James E. and Trapp, Stefan (2018) GLP-1 action in the mouse bed nucleus of the stria terminalis. Neuropharmacology, 131 . pp. 83-95. doi:10.1016/j.neuropharm.2017.12.007 ISSN 0028-3908.
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Official URL: https://doi.org/10.1016/j.neuropharm.2017.12.007
Abstract
Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression. The BNST displayed many varicose YFP+ PPG axons in the ventral and less in the dorsal regions. Mice which express RFP in GLP-1R neurons had RFP+ cells throughout the BNST with the highest density in the dorsal part, suggesting that PPG neuron-derived GLP-1 acts in the BNST. Indeed, injection of GLP-1 into the BNST reduced chow intake during the dark phase, whereas injection of the GLP-1 receptor antagonist Ex9 increased feeding. BNST-specific GLP-1-induced food suppression was less effective in mice on high fat (HF, 60%) diet, and Ex9 had no effect. Restraint stress-induced hypophagia was attenuated by BNST Ex9 treatment, further supporting a role for endogenous brain GLP-1. Finally, whole-cell patch clamp recordings of RFP+ BNST neurons demonstrated that GLP-1 elicited either a depolarizing or hyperpolarizing reversible response that was of opposite polarity to that under dopamine. Our data support a physiological role for BNST GLP-1R in feeding, and suggest complex cellular responses to GLP-1 in this nucleus.
Item Type: | Journal Article | ||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||
Library of Congress Subject Headings (LCSH): | Glucagon-like peptide 1, Electrophysiology , Proteins | ||||||||||||
Journal or Publication Title: | Neuropharmacology | ||||||||||||
Publisher: | Elsevier | ||||||||||||
ISSN: | 0028-3908 | ||||||||||||
Official Date: | 15 March 2018 | ||||||||||||
Dates: |
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Volume: | 131 | ||||||||||||
Page Range: | pp. 83-95 | ||||||||||||
DOI: | 10.1016/j.neuropharm.2017.12.007 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | Published | ||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
Date of first compliant deposit: | 19 January 2024 | ||||||||||||
Date of first compliant Open Access: | 19 January 2024 | ||||||||||||
RIOXX Funder/Project Grant: |
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