Atlas of GLP-1 expression in the mouse brain: Neuroanatomical basis for metabolic and psychiatric effects

Recently, glucagon-like peptide 1 (GLP-1) and its new blockbuster class of analogs have emerged as powerful therapeutics to combat obesity and diabetes, with growing evidence for potential efficacy in addiction, depression, and other psychiatric conditions. Although metabolic diseases are common in both women and men, certain pathological and clinical features exhibit sex-specific differences, as do psychiatric disorders. Importantly, as part of a broader network of peptides and hormones regulating ingestive and reward-related behaviors, GLP-1 appears to have stronger effects on appetite suppression, glycemic regulation, and body weight loss in females compared with males-though sex differences in its psychiatric effects remain underexplored. We utilized RNAscope to create a comprehensive atlas of sex-specific (n = 3 per sex) GLP-1 expressing sites in the murine brain. Notably, in the hindbrain, Glp1 densities and total numbers of Glp1-expressing neurons in the raphe obscurus nucleus, ventral and ventrolateral parts of the solitary nucleus were higher in females compared with males. In the olfactory bulb, Glp1 densities were greater in the granular cell layer of males in comparison with females. Collectively, this atlas should serve as a resource to advance our understanding of GLP-1's central functions in both metabolic and psychiatric contexts.