Endocrine Abstracts

Glucagon-like peptide 1 (GLP1) acts as both a peripheral incretin hormone and a central neuropeptide to regulate glucose and energy homeostasis. Within the brain, GLP1 is synthesised by a discrete collection of neurones in the brainstem, and presynaptic release of GLP1 results in binding to postsynaptic GLP1 receptors (GLP1R). The pattern of projections from these GLP1 synthesising neurones in the mouse brain has been described previously^1,2. Here we use a novel transgenic mouse expressing Cre under the control of the GLP1R promotor with an ROSA26-tdRFP reporter to investigate brain regions which express the receptor for GLP1. GLP1R-Cre mice were transcardially perfused with 0.1 M PB followed by 4% paraformaldehyde. Brains were removed and sectioned to 30 μm before immunofluorescent detection of tdRFP. RFP-positive cells were found throughout the rostrocaudal extent of the brain in areas which correlate with those previously reported in rat³. Specifically, high levels of RFP-positive cells were found in the dorsomedial hypothalamus, paraventricular nucleus of the hypothalamus, ventral tegmental area, and area postrema. This also correlates with areas which receive high levels of input from GLP1 neurones². Interestingly, RFP positive neurones were also found in areas devoid of PPG-neurone projections, such as the hippocampus and cortex, raising the question whether these areas may respond to GLP1 of non-neuronal origin. The results from this study provide further information regarding the distribution of GLP1Rs in the mammalian brain. Furthermore, the use of Cre in neurones expressing GLP1R provides a molecular handle on these neurones in future investigations.

References: 1. Llewellyn-Smith et al. Neuroscience 2011 180 111–121.

2. Llewellyn-Smith et al. Neuroscience 2013 229 130–143.

3. Merchenthaler et al. J Comp Neurol 1999 403 261–280.