FASTING INDUCES REMODELING OF THE OREXIGENIC PROJECTIONS FROM THE ARCUATE NUCLEUS TO THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS IN A GROWTH HORMONE SECRETAGOGUE RECEPTOR-DEPENDENT MANNER

GIMENA FERNANDEZ | AGUSTINA CABRAL | TOLOSA MARÍA JOSE | REY-MOGGIA ÁNGELES | DE FRANCESCO PABLO NICOLAS | GARCÍA ROMERO GUADALUPE | REYNALDO MIRTA | CALFA GASTÓN | PERELLO MARIO

Mar del Plata

Congreso; Reunion Anual de Sociedades de Biociencia SAIC, SAFE, SAB, SAP; 2019

Sociedades de Biociencia

Some hypothalamic circuits are known to undergo morphological and functional remodeling in order to ensure the control of the body homeostasis. Ghrelin is a stomach-derived hormone that acts on the growth hormone secretagogue receptor (GHSR), and is known to play a key regulatory role on the energy balance. Here, we hypothesized that the up-regulation of the GHSR system during fasting at the orexigenic Agouti-related peptide (AgRP)/neuropeptide Y (NPY)-producing neurons of the arcuate nucleus (ARC) would promote a morphological remodeling of the ARC projections to the hypothalamic paraventricular nucleus (PVH) in adult mice, and that such structural changes mediate the fasting-induced activation of the PVH neurons. We showed through immunostaining analysis that the total amount of the orexigenic neuropeptides AgRP and NPY (mean intensity), the density of fibers containing these neuropeptides (area) and the amount of AgRP and NPY per fiber (integrated density) were increased in the PVH of fasted mice. Similarly, analysis of fluorescent signal in the PVH of NPY-GFP mice also showed that ARCNPY→PVH projections increase under fasting. In addition, tracing studies confirmed that ARC→PVH projections increase under fasting. Importantly, fasting-induced activation of PVH neurons was impaired in ARC-ablated mice in which the density and strength of ARCAgRP/NPY→PVH projections is not increased under fasting. Additionally, we show that fasting-induced remodeling of these projections from the ARC to the PVH and the fasting-induced activation of the PVH neurons is impaired in mice with pharmacological or genetic blockage of the GHSR signaling suggesting that ghrelin signaling controls these adaptations. To our knowledge, these are the first evidence that the connectivity between hypothalamic circuits controlling food intake can be remodeled in the adult brain, depending on the energy balance conditions, and that GHSR activity is a key regulator of this phenomenon.