Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS
Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS
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DOI：
10.1016/j.neuron.2010.08.007
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发表时间：
2010-09-09
期刊：
影响因子：
16.2
通讯作者：
Torres-Aleman, Ignacio
中科院分区：
文献类型：
--
作者：
Nishijima, Takeshi;Piriz, Joaquin;Torres-Aleman, Ignacio
在进入中枢神经系统（CNS）后，血清胰岛素样生长因子-1 （IGF-I）调节神经元的生长、存活和兴奋性。然而，触发igf - 1进入血脑屏障的机制尚不清楚。我们发现，由电刺激、感觉刺激或行为刺激引起的神经元活动增加了激活区域的igf - 1输入。血清IGF-I的进入是由神经血管耦合过程中释放的弥散性信使（即ATP、花生四烯酸衍生物）触发的。这些信使刺激基质金属蛋白酶-9，导致IGF结合蛋白-3 （IGFBP-3）的断裂。IGFBP-3的切割允许血清igf - 1通过与内皮转运体脂蛋白相关受体1的相互作用进入中枢神经系统。血清igf - 1进入中枢神经系统的活性依赖性可能有助于解释不同的观察结果，如癫痫的前神经源性作用、神经刺激的康复作用和血流对脑活动的调节作用。
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.