Cork, SC;
Richards, JE;
Holt, MK;
Gribble, FM;
Reimann, F;
Trapp, S;
(2015)
Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain.
Molecular Metabolism
, 4
(10)
pp. 718-731.
10.1016/j.molmet.2015.07.008.
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Abstract
Objective: Although Glucagon-like peptide 1 is a key regulator of energy metabolism and food intake, the precise location of GLP-1 receptors and the physiological relevance of certain populations is debatable. This study investigated the novel GLP-1R-Cre mouse as a functional tool to address this question. Methods: Mice expressing Cre-recombinase under the Glp1r promoter were crossed with either a ROSA26 eYFP or tdRFP reporter strain to identify GLP-1R expressing cells. Patch-clamp recordings were performed on tdRFP-positive neurons in acute coronal brain slices from adult mice and selective targeting of GLP-1R cells invivo was achieved using viral gene delivery. Results: Large numbers of eYFP or tdRFP immunoreactive cells were found in the circumventricular organs, amygdala, hypothalamic nuclei and the ventrolateral medulla. Smaller numbers were observed in the nucleus of the solitary tract and the thalamic paraventricular nucleus. However, tdRFP positive neurons were also found in areas without preproglucagon-neuronal projections like hippocampus and cortex. GLP-1R cells were not immunoreactive for GFAP or parvalbumin although some were catecholaminergic. GLP-1R expression was confirmed in whole-cell recordings from BNST, hippocampus and PVN, where 100nM GLP-1 elicited a reversible inward current or depolarisation. Additionally, a unilateral stereotaxic injection of a cre-dependent AAV into the PVN demonstrated that tdRFP-positive cells express cre-recombinase facilitating virally-mediated eYFP expression. Conclusions: This study is a comprehensive description and phenotypic analysis of GLP-1R expression in the mouse CNS. We demonstrate the power of combining the GLP-1R-CRE mouse with a virus to generate a selective molecular handle enabling future invivo investigation as to their physiological importance.
| Type: | Article |
|---|---|
| Title: | Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.molmet.2015.07.008 |
| Publisher version: | http://dx.doi.org/10.1016/j.molmet.2015.07.008 |
| Language: | English |
| Additional information: | This is an open access article licensed under a Creative Commons Attribution 4.0 International License. See <http://creativecommons.org/licenses/by/4.0/>. |
| Keywords: | Channelrhodopsin, Electrophysiology, GLP-1, Glucagon-like peptide-1 receptor, PPG, Preproglucagon |
| 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/1470355 |
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