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Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain.

Title: Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain.
Authors: Cork, SC
Richards, JE
Holt, MK
Gribble, FM
Reimann, F
Trapp, S
Item Type: Journal Article
Abstract: © 2015 The Authors.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 in vivo 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 100 nM 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 in vivo investigation as to their physiological importance.
Issue Date: 1-Oct-2015
Date of Acceptance: 28-Jul-2015
URI: http://hdl.handle.net/10044/1/28492
DOI: https://dx.doi.org/10.1016/j.molmet.2015.07.008
ISSN: 2212-8778
Publisher: Elsevier
Start Page: 718
End Page: 731
Journal / Book Title: Molecular Metabolism
Volume: 4
Issue: 10
Copyright Statement: © 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Medical Research Council (MRC)
Diabetes UK
Funder's Grant Number: MR/J013293/1
Keywords: AP, area postrema
BNST, bed nucleus stria terminalis
DMH, dorsomedial nucleus of the hypothalamus
DMV, dorsal motor nucleus of the vagus
Ex-4, Exendin-4
GFAP, glial fibrillary acidic protein
GFP, green fluorescent protein
GLP-1, Glucagon-like peptide-1
GLP-1R, Glucagon-like peptide-1 receptor
Glucagon-like peptide-1 receptor
NAc, nucleus accumbens
NTS, nucleus of the solitary tract
PARV, parvalbumin
PPG, preproglucagon
PVN, paraventricular nucleus of the hypothalamus
TH, tyrosine hydroxylase
VTA, ventral tegmental area
YFP, yellow fluorescent protein
Publication Status: Published
Appears in Collections:Department of Medicine (up to 2019)