ANALYSIS OF THE MORPHOLOGICAL REMODELING OF OREXIGENIC AGRP FIBERS IN THE BRAIN OF FASTED MICE: A POTENTIAL REGULATORY ROLE OF THE GHRELIN SIGNALING

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

Congreso; XXXV Reunión Anual SAN2020; 2020

Agouti-related peptide-producing neurons of the arcuate nucleus (ARCAgRP neurons), which innervate several appetite-related brain regions, are activated in fasting states. Recently, we found that the ARCAgRP projections to the hypothalamic paraventricular nucleus 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 (lateral hypothalamic area, LHA) and extra-hypothalamic (paraventricular thalamus, PVT, and central amygdala, CeA) ARCAgRP projections and its dependence on GHSR. We performed fluorescent immunostaining against AgRP in brains of ad libitum fed or fasted mice with pharmacological or genetic blockage of the GHSR signaling and estimated the density and strength of ARCAgRP fibers. We found that: 1) the density and strength of ARCAgRP fibers increase in the LHA of fasted mice, whereas no differences were detected in the PVT and CeA. 2) Fasting-induced increase of the marker of neuronal activation c-Fos in the LHA was abrogated in ARC-ablated mice. 3) Fasting-induced remodeling of ARCAgRP→LHA projections was not affected in mice with pharmacological or genetic blockage of GHSR signaling. This evidence shows that the remodeling of the ARCAgRP fibers in fasting state occurs in a brain region-dependent manner and that the GHSR activity does not regulate this phenomenon in the LHA.