Ghrelin regulates divergent neuronal circuits within the dorsal vagal complex

CORNEJO MP; CABRAL A; DE FRANCESCO PN; FERNANDEZ G; VALDIVIA S; GARCIA ROMERO G; REYNALDO M; PERELLO M

Mendoza

Workshop; International Workshop of Neuroendocrinology; 2015

The dorsal vagal complex (DVC) of the brainstem includes the nucleus of the solitary tract (NTS), the area postrema (AP), and the dorsal motor nucleus of the vagus (10N). The DVC is an integrative center that regulates food intake and also relays autonomic neural circuits that control many key functions including blood glucose concentration, blood pressure, gastro-intestinal motility, among others. The growth hormone secretagogue receptor (GHSR), which is the target of the hormone ghrelin, is expressed in the DVC. Given the technical difficulties to identify GHSR by traditional techniques, the detailed neuroanatomical distribution of GHSR-expressing neurons within the DVC and the physiological role of ghrelin signaling on this brain area are unclear.In the current study, we performed a detailed neuroanatomical characterization of the distribution of GHSR within the DVC using a transgenic mice in which the green fluorescent protein (GFP) is under the control of the GHSR promoter (GHSR-GFP mice). Also, we performed immunohistochemistry (IHC) with markers of specific neuronal populations in order to characterize the phenotype of the GHSR-expressing neurons. Finally, we used fluorescein-ghrelin (F-ghrelin, as a tracer peptide) and the marker of cellular activation c-Fos to study the responsiveness of GHSR-expressing neurons of the DVC to ghrelin. Based on the results obtained we can confirm that:- GHSR-expressing neurons are present in all three components of the DVC and are enriched in the AP.- The phenotype of GHSR-expressing neurons of the DVC remains to be elucidated.- Peripheral ghrelin would activate GHSR-expressing neurons of the AP directly while peripheral ghrelin would be unable to reach the NTS and, as a consequence, GHSR-expressing neurons of the NTS could not respond directly to the hormone. However, a subset of NTS neurons could respond indirectly to peripheral ghrelin via the initial activation of GHSR-expressing neurons of the AP that innervate the NTS. Ghrelin present in the cerebrospinal fluid can accesses not only to the AP but also to the NTS, where it directly activates GHSR-expressing neurons of the anterior and posterior levels of this nucleus. NTS neurons that respond to ghrelin via direct and indirect mechanisms may have different physiological roles.