Analysis of the morphological remodeling of orexigenic AgRP fibers in the brain of fasted mice: A potential regulatory role of the Ghrelin signaling

DANIELA ALEJANDRA CASSANO, GIMENA FERNANDEZ, PABLO NICOLAS DE FRANCESCO, GUADALUPE GARCÍA ROMERO, MARIA JOSE TOLOSA, MIRTA REYNALDO, MARIO PERELLO

Congreso; XXXV Reunión Anual SAN2020; 2020

Agouti-related peptide-producing neurons of the arcuate nucleus (ARC-AgRP neurons),which innervate several appetite-related brain regions, are activated in fasting states.Recently, we found that the ARC-AgRP projections to the hypothalamic paraventricularnucleus are remodeled in fasting states in a growth hormone secretagogue receptor(GHSR)-dependent manner. Here, we tested if the fasting-induced activation of ARCAgRP neurons promotes morphological remodeling of other hypothalamic (lateralhypothalamic area, LHA) and extra-hypothalamic (paraventricular thalamus, PVT, andcentral amygdala, CeA) ARC-AgRP projections and its dependence on GHSR. Weperformed fluorescent immunostaining against AgRP in brains of ad libitum fed or fastedmice with pharmacological or genetic blockage of the GHSR signaling and estimated thedensity and strength of ARC-AgRP fibers. We found that: 1) the density and strength ofARC-AgRP fibers increase in the LHA of fasted mice, whereas no differences weredetected in the PVT and CeA. 2) Fasting-induced increase of the marker of neuronalactivation c-Fos in the LHA was abrogated in ARC-ablated mice. 3) Fasting-inducedremodeling of ARC-AgRP→LHA projections was not affected in mice withpharmacological or genetic blockage of GHSR signaling. This evidence shows that theremodeling of the ARC-AgRP fibers in fasting state occurs in a brain region-dependentmanner and that the GHSR activity does not regulate this phenomenon in the LHA