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Title

Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS

AuthorsNishijima, T.; Piriz, Joaquin ; Duflot, Sylvie; Fernández García, Ana María ; Gaitán, Gema; Gómez-Pinedo, Ulises; García-Verdugo, José M.; Leroy, Félix; Soya, Hideaki; Núñez Molina, Ángel; Torres Alemán, Ignacio
KeywordsSysneuro
Molneuro
Signaling
Issue Date9-Sep-2010
PublisherElsevier
CitationNeuron 67(5): 834-846 (2010)
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.
Publisher version (URL)http://dx.doi.org/10.1016/j.neuron.2010.08.007
URIhttp://hdl.handle.net/10261/27623
DOI10.1016/j.neuron.2010.08.007
ISSN0896-6273
Appears in Collections:(IC) Artículos
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