6533b7d3fe1ef96bd1261605

RESEARCH PRODUCT

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

José Manuel García VerdugoUlises Gómez-pinedoIgnacio Torres-alemanJoaquin PirizTakeshi NishijimaAna M. FernandezAngel NuñezFelix LeroyHideaki SoyaSylvie DuflotGema Gaitan

subject

Central Nervous SystemTime FactorsMicrodialysismedicine.medical_treatmentAction PotentialsStimulationFunctional LateralityBody TemperatureReceptor IGF Type 1chemistry.chemical_compoundNeural PathwaysPremovement neuronal activityDrug InteractionsInsulin-Like Growth Factor IMicroscopy ImmunoelectronReceptorCells CulturedNeuronsGeneral NeuroscienceSysneuro//purl.org/becyt/ford/3.1 [https]Protein TransportMedicina Básicamedicine.anatomical_structureMatrix Metalloproteinase 9Blood-Brain BarrierSIGNALING//purl.org/becyt/ford/3 [https]Arachidonic acidNeurogliaLow Density Lipoprotein Receptor-Related Protein-1CIENCIAS MÉDICAS Y DE LA SALUDNeuroscience(all)Central nervous systemNeurocienciasBiophysicsGlutamic AcidEnzyme-Linked Immunosorbent AssayNerve Tissue ProteinsBiologyBlood–brain barrierMOLNEUROmedicineAnimalsHumansImmunoprecipitationRats WistarAnalysis of VarianceGrowth factorEndothelial CellsTransporterCoculture TechniquesElectric StimulationSignalingRatsMolneurochemistryRegional Blood FlowVibrissaeSYSNEURODigoxigeninExcitatory Amino Acid AntagonistsNeuroscience

description

Upon 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.

yearjournalcountryeditionlanguage
2010-09-01
10.1016/j.neuron.2010.08.007http://hdl.handle.net/10261/27623