Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. (Articolo in rivista)

Type
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  • Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1073/pnas.1219485110 (literal)
Alternative label
  • Cristino L.(a,f), Busetto G.(b,c), Imperatore R. (a,f),Ferrandino I.(d), Palomba L. (a,e), Silvestri C. (f), Petrosino S.(f), Orlando P. (g), Bentivoglio M. (b), Mackie K. (h), Di Marzo V. (f) (2013)
    Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons.
    in Proceedings of the National Academy of Sciences of the United States of America (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cristino L.(a,f), Busetto G.(b,c), Imperatore R. (a,f),Ferrandino I.(d), Palomba L. (a,e), Silvestri C. (f), Petrosino S.(f), Orlando P. (g), Bentivoglio M. (b), Mackie K. (h), Di Marzo V. (f) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 110 (literal)
Rivista
Note
  • ISI Web of Science (WOS (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • (a) LUIGIA CRISTINO: Endocannabinoid Research Group, Institute of Cybernetics \"Eduardo Caianiello\", Consiglio Nazionale delle Ricerche, Viale Campi Flegrei 34, 80078 Pozzuoli, Italy, b Department of Neurological Sciences (DSNNMM), University of Verona, Strada Le Grazie 8, 37134 Verona, Italy, c National Institute of Neuroscience, Strada Le Grazie 8, 37134 Verona, Italy, d Department of Biological Sciences, University Federico II, Via Mezzocannone 16, 80134 Napoli, Italy, e Endocannabinoid Research Group, Department of Biomolecular Sciences, University \"Carlo Bo\", Via S. Chiara, 27 61029 Urbino, Italy, f Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Viale Campi Flegrei 34, 80078 Pozzuoli, Italy, g Endocannabinoid Research Group, Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via Castellino 111, 80131 Napoli, Italy, h Department of Psychological and Brain Sciences and Gill Center, Indiana University, 47405-7000 Bloomington, USA. (literal)
Titolo
  • Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. (literal)
Abstract
  • Acute or chronic alterations in energy status alter the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity to allow for the adaptation of energy metabolism to new homeostatic requirements. The impact of such changes on endocannabinoid and CB1 receptor-mediated modulation of synaptic transmission and strength is not known, despite the fact that this signaling system is an important target for the development of new drugs against obesity. We investigated whether CB1-expressing excitatory versus inhibitory inputs to orexin-A-containing neurons in the lateral hypothalamus are altered in obesity and how this modifies endocannabinoid control of these neurons. In lean mice, these inputs are mostly excitatory. By confocal and ultrastructural microscopic analyses, we observed that in leptin-knockout (ob/ob) obese mice, and in mice with diet-induced obesity, orexinergic neurons receive predominantly inhibitory CB1-expressing inputs and overexpress the biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol, which retrogradely inhibits synaptic transmission at CB1-expressing axon terminals. Patch-clamp recordings also showed increased CB1-sensitive inhibitory innervation of orexinergic neurons of ob/ob mice. These alterations are reversed by leptin administration, partly through activation of the mammalian target of rapamycin pathway in NPYergic neurons of the arcuate nucleus, and are accompanied by CB1-mediated enhancement of orexinergic innervation of target brain areas. We propose that enhanced inhibitory control of orexin-A neurons, and their CB1-mediated disinhibition, are a consequence of leptin signaling impairment in the arcuate nucleus. We also provide initial evidence of the participation of this phenomenon in hyperphagia and hormonal dysregulation in obesity. (literal)
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