TY - JOUR
T1 - Ghrelin receptor signaling targets segregated clusters of neurons within the nucleus of the solitary tract
AU - Cornejo, María Paula
AU - De Francesco, Pablo Nicolás
AU - García Romero, Guadalupe
AU - Portiansky, Enrique L.
AU - Zigman, Jeffrey M.
AU - Reynaldo, Mirta
AU - Perello, Mario
N1 - Funding Information:
Funding This work was funded by the PICTO2013-0065 grant, which is co-financed by the National Agency of Scientific and Technological Promotion of Argentina and GlaxoSmithKline, to MP.
Funding Information:
MPC was supported by CONICET. The authors declare that they have no conflict of interest.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Ghrelin is a stomach-derived hormone that regulates a variety of biological functions such as food intake, gastrointestinal function and blood glucose metabolism, among others. Ghrelin acts via the growth hormone secretagogue receptor (GHSR), a G-protein-coupled receptor located in key brain areas that mediate specific actions of the hormone. GHSR is highly expressed in the nucleus of the solitary tract (NTS), which is located in the medulla oblongata and controls essential functions, including orofacial, autonomic, neuroendocrine and behavioral responses. Here, we used a mouse model, in which the expression of enhanced green fluorescent protein (eGFP) is controlled by the promoter of GHSR (GHSR-eGFP mice), to gain neuroanatomical and functional insights of the GHSR-expressing neurons of the NTS. We found that GHSR-expressing neurons of the NTS are segregated in clusters that were symmetrically distributed to the midline: (1) a pair of rostral clusters, and (2) a caudal and medially located cluster. We also identified that a subset of GHSR neurons of the caudal NTS are GABAergic. Finally, we found that rostral NTS GHSR neurons increase the levels of the marker of neuronal activation c-Fos in mice exposed to fasting/refeeding or high-fat diet bingeing protocols, while caudal NTS GHSR neurons increase the levels of c-Fos in mice exposed to gastric distension or LiCl-induced malaise protocols. Thus, current data provide evidence that ghrelin receptor signaling seems to target segregated clusters of neurons within the NTS that, in turn, may be activated by different stimuli.
AB - Ghrelin is a stomach-derived hormone that regulates a variety of biological functions such as food intake, gastrointestinal function and blood glucose metabolism, among others. Ghrelin acts via the growth hormone secretagogue receptor (GHSR), a G-protein-coupled receptor located in key brain areas that mediate specific actions of the hormone. GHSR is highly expressed in the nucleus of the solitary tract (NTS), which is located in the medulla oblongata and controls essential functions, including orofacial, autonomic, neuroendocrine and behavioral responses. Here, we used a mouse model, in which the expression of enhanced green fluorescent protein (eGFP) is controlled by the promoter of GHSR (GHSR-eGFP mice), to gain neuroanatomical and functional insights of the GHSR-expressing neurons of the NTS. We found that GHSR-expressing neurons of the NTS are segregated in clusters that were symmetrically distributed to the midline: (1) a pair of rostral clusters, and (2) a caudal and medially located cluster. We also identified that a subset of GHSR neurons of the caudal NTS are GABAergic. Finally, we found that rostral NTS GHSR neurons increase the levels of the marker of neuronal activation c-Fos in mice exposed to fasting/refeeding or high-fat diet bingeing protocols, while caudal NTS GHSR neurons increase the levels of c-Fos in mice exposed to gastric distension or LiCl-induced malaise protocols. Thus, current data provide evidence that ghrelin receptor signaling seems to target segregated clusters of neurons within the NTS that, in turn, may be activated by different stimuli.
KW - Dorsal vagal complex
KW - GABA neurons
KW - Medulla oblongata
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U2 - 10.1007/s00429-018-1682-5
DO - 10.1007/s00429-018-1682-5
M3 - Article
C2 - 29761230
AN - SCOPUS:85052577163
VL - 223
SP - 3133
EP - 3147
JO - Brain Structure and Function
JF - Brain Structure and Function
SN - 1863-2653
IS - 7
ER -