Topography of the GLP-1/GLP-1 receptor system in the spinal cord of male mice

Ruska, Yvette Magdolna and Csibi, Andrea and Dorogházi, Beáta Vanessza and Stiftné Szilvásy-Szabó, Anett and Mohácsik, Petra and Környei, Zsuzsanna and Dénes, Ádám and Kádár, Andrea and Puskár, Zita and Hrabovszky, Erik and Gereben, Balázs and Wittmann, Gábor and Fekete, Csaba (2024) Topography of the GLP-1/GLP-1 receptor system in the spinal cord of male mice. SCIENTIFIC REPORTS, 14 (1). No. 14403. ISSN 2045-2322

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Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonists are now commonly used to treat type 2 diabetes and obesity. GLP-1R signaling in the spinal cord has been suggested to account for the mild tachycardia caused by GLP-1R agonists, and may also be involved in the therapeutic effects of these drugs. However, the neuroanatomy of the GLP-1/GLP-1R system in the spinal cord is still poorly understood. Here we applied in situ hybridization and immunohistochemistry to characterize this system, and its relation to cholinergic neurons. GLP-1R transcript and protein were expressed in neuronal cell bodies across the gray matter, in matching distribution patterns. GLP-1R-immunolabeling was also robust in dendrites and axons, especially in laminae II–III in the dorsal horn. Cerebrospinal fluid-contacting neurons expressed GLP-1R protein at exceedingly high levels. Only small subpopulations of cholinergic neurons expressed GLP-1R, including a subset of sympathetic preganglionic neurons at the rostral tip of the intermediolateral nucleus. GLP-1 axons innervated all regions where GLP-1R neurons were distributed, except laminae II–III. Scattered preproglucagon ( Gcg ) mRNA-expressing neurons were identified in the cervical and lumbar enlargements. The results will facilitate further studies on how GLP-1 regulates the sympathetic system and other autonomic and somatic functions via the spinal cord.

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