info:eu-repo/semantics/article
Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS
Fecha
2010-09Registro en:
Nishijima, Takeshi; Piriz, Joaquin; Duflot, Sylvie; Fernandez, Ana M.; Gaitan, Gema; et al.; Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS; Cell Press; Neuron; 67; 5; 9-2010; 834-846
0896-6273
CONICET Digital
CONICET
Autor
Nishijima, Takeshi
Piriz, Joaquin
Duflot, Sylvie
Fernandez, Ana M.
Gaitan, Gema
Gomez Pinedo, Ulises
Verdugo, Jose M. Garcia
Leroy, Felix
Soya, Hideaki
Nuñez, Angel
Torres Aleman, Ignacio
Resumen
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.