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: | Gimena Fernandez, Mario Perello, Pablo Nicolás de Francesco, Gaston Diego Calfa, Agustina Cabral, Maria Jose Tolosa, Ángeles Rey Moggia |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine medicine.medical_specialty Growth hormone secretagogue receptor 030209 endocrinology & metabolism Green fluorescent protein 03 medical and health sciences Mice 0302 clinical medicine Arcuate nucleus Food intake Internal medicine Orexigenic AgRP/NPY neurons mental disorders medicine Animals lcsh:RC31-1245 Receptors Ghrelin Molecular Biology Mice Knockout Arc (protein) Chemistry digestive oral and skin physiology Arcuate Nucleus of Hypothalamus purl.org/becyt/ford/3.1 [https] Cell Biology Fasting Neuropeptide Y receptor humanities Ghrelin Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology purl.org/becyt/ford/3 [https] Original Article Nucleus medicine.drug Paraventricular Hypothalamic Nucleus |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 32, Iss, Pp 69-84 (2020) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 2212-8778 |
| Popis: | Objective Arcuate nucleus (ARC) 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. Methods We performed 1) fluorescent immunohistochemistry, 2) imaging of green fluorescent protein (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 the fluorescent signal in the fluorescent area of the PVH. Results 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. We also found that fasting-induced remodeling of ARCAgRP/NPY→PVH fibers and PVH activation are impaired in mice with pharmacological or genetic blockage of GHSR signaling. Conclusion 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. Graphical abstract Image 1 HIGHLIGHTS • The density and strength of ARCAgRP/NPY→PVH fibers increase in fasted mice. • Remodeling of ARCAgRP/NPY→PVH projections correlates with the activation of PVH neurons. • GHSR signaling is required for fasting-induced ARCAgRP/NPY→PVH projection remodeling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|