Imperial College London
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Dr Simon C. Cork, PhD, FHEA

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 7848 8044simon.cork

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cork:2015:10.1016/j.molmet.2015.07.008,
author = {Cork, SC and Richards, JE and Holt, MK and Gribble, FM and Reimann, F and Trapp, S},
doi = {10.1016/j.molmet.2015.07.008},
journal = {Molecular Metabolism},
pages = {718--731},
title = {Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain.},
url = {http://dx.doi.org/10.1016/j.molmet.2015.07.008},
volume = {4},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Cork,SC
AU  - Richards,JE
AU  - Holt,MK
AU  - Gribble,FM
AU  - Reimann,F
AU  - Trapp,S
DO  - 10.1016/j.molmet.2015.07.008
EP  - 731
PY  - 2015///
SN  - 2212-8778
SP  - 718
TI  - Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain.
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2015.07.008
UR  - http://hdl.handle.net/10044/1/28492
VL  - 4
ER  -
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