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

Oct 27, 2015Molecular metabolism

Location and features of brain cells with glucagon-like peptide-1 receptors in mice

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Large numbers of GLP-1 receptor (GLP-1R) expressing cells were identified in key brain regions such as the circumventricular organs and amygdala.

GLP-1R expressing neurons were found in regions associated with energy metabolism and food intake regulation.
Smaller populations of GLP-1R cells were observed in the nucleus of the solitary tract and the thalamic paraventricular nucleus.
Some tdRFP positive neurons were located in the hippocampus and cortex, areas without preproglucagon-neuronal projections.
GLP-1R cells did not show immunoreactivity for astrocyte markers or parvalbumin, but some were identified as catecholaminergic.
Whole-cell recordings confirmed GLP-1R expression and responsiveness to GLP-1 in the BNST, hippocampus, and PVN.

AI simplified

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.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (XML) ↗View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief