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dc.contributor.authorNishijima, T.-
dc.contributor.authorPiriz, Joaquin-
dc.contributor.authorDuflot, Sylvie-
dc.contributor.authorFernández García, Ana María-
dc.contributor.authorGaitán, Gema-
dc.contributor.authorGómez-Pinedo, Ulises-
dc.contributor.authorGarcía-Verdugo, José M.-
dc.contributor.authorLeroy, Félix-
dc.contributor.authorSoya, Hideaki-
dc.contributor.authorNúñez Molina, Ángel-
dc.contributor.authorTorres Alemán, Ignacio-
dc.date.accessioned2010-09-14T11:04:10Z-
dc.date.available2010-09-14T11:04:10Z-
dc.date.issued2010-09-09-
dc.identifier.citationNeuron 67(5): 834-846 (2010)en_US
dc.identifier.issn0896-6273-
dc.identifier.urihttp://hdl.handle.net/10261/27623-
dc.description.abstractUpon entry into the central nervous system (CNS), serum insulin-like growth factor-1 (IGF-I) modulates neuronal growth, survival, and excitability. Yet mechanisms that trigger IGF-I entry across the blood-brain barrier remain unclear. We show that neuronal activity elicited by electrical, sensory, or behavioral stimulation increases IGF-I input in activated regions. Entrance of serum IGF-I is triggered by diffusible messengers (i.e., ATP, arachidonic acid derivatives) released during neurovascular coupling. These messengers stimulate matrix metalloproteinase-9, leading to cleavage of the IGF binding protein-3 (IGFBP-3). Cleavage of IGFBP-3 allows the passage of serum IGF-I into the CNS through an interaction with the endothelial transporter lipoprotein related receptor 1. Activity-dependent entrance of serum IGF-I into the CNS may help to explain disparate observations such as proneurogenic effects of epilepsy, rehabilitatory effects of neural stimulation, and modulatory effects of blood flow on brain activity.en_US
dc.description.sponsorshipThis work was funded by Spanish Ministry of Science (SAF2007-60051), by CIBERNED, and by a joint Japan-Spain collaborative program (JSPS-CSIC-2006JP0010). I.T.-A. is founder of a company (9% ownership) devoted to the use of IGF-I for neurodegenerative diseases.en_US
dc.format.extent615940 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsopenAccessen_US
dc.subjectSysneuroen_US
dc.subjectMolneuroen_US
dc.subjectSignaling-
dc.titleNeuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNSen_US
dc.typeartículoen_US
dc.identifier.doi10.1016/j.neuron.2010.08.007-
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.neuron.2010.08.007en_US
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