IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Fasting Induces Remodeling of the Orexigenic Projections from the Arcuate Nucleus to the Hypothalamic Paraventricular Nucleus, in a Growth Hormone Secretagogue Receptor-Dependent Manner
Autor/es:
GIMENA FERNANDEZ; ÁNGELES REY-MOGGIA; MIRTA REYNALDO; AGUSTINA CABRAL; GASTÓN CALFA; MARÍA JOSE TOLOSA; NICOLAS DE FRANCESCO; GUADALUPE GARCÍA ROMERO; MARIO PERELLO
Reunión:
Congreso; Reunión Anual de Sociedades de Biociencia; 2019
Resumen:
Arcuate nucleus neurons producing Agouti-related peptide (AgRP) and neuropeptide Y (NPY) (ARCAgRP/NPY neurons) are activated under energy deficit states. ARCAgRP/NPY neurons innervate the hypothalamic paraventricular nucleus (PVH), and ARC→PVH projections are recognized as key regulators of food intake. Plasma ghrelin levels increase under energy deficit states and activate ARCAgRP/NPY neurons by acting on the growth hormone secretagogue receptor (GHSR). Here, we hypothesized that activation of ARCAgRP/NPY neurons in fasted mice would promote morphological remodeling of the ARCAgRP/NPY→PVH projections in a GHSR-dependent manner. Here, we performed 1) fluorescent immunohistochemistry, 2) imaging of GFP signal in NPY-GFP mice and 3) DiI axonal labeling in brains of ad libitum fed or fasted mice with pharmacological or genetic blockage of the GHSR signaling, and then estimated the density and strength of ARCAgRP/NPY→PVH fibers by assessing the mean fluorescence intensity, the absolute area with fluorescent signal and the intensity of fluorescent signal in the fluorescent area of the PVH. We found that: 1) the density and strength of ARCAgRP/NPY fibers increase in the PVH of fasted mice, 2) the morphological remodeling of the ARCAgRP/NPY→PVH projections correlates with the activation of PVH neurons, and 3) PVH neurons are not activated in ARC-ablated mice. Also, we found that fasting-induced remodeling of ARCAgRP/NPY→PVH fibers and PVH activation is impaired in mice with pharmacological or genetic blockage of GHSR signaling. This evidence shows 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.