Drugs improve mouse cognitive function by increasing the production of insulin-like growth factor-I

胰岛素样生长因子-I(IGF-I)对认知功能有有益的影响。由于感觉神经元的刺激通过在小鼠脑内释放降钙素基因相关肽(CGRP)来诱导IGF-I的产生，我们推测多奈哌齐除了抑制乙酰胆碱酯酶外，还可能对感觉神经元有刺激作用，从而通过增加海马区IGF-I的产生来促进血管生成和神经发生。为了验证这种可能性，我们分析了两种选择性乙酰胆碱酯酶抑制剂(多奈哌齐和他克林)对WT小鼠、CGRP基因敲除[CGRP(-/-)]小鼠和因新生儿注射辣椒素导致功能性感觉失神经的WT小鼠海马IGF-I产生和认知功能的影响。

Insulin-like growth factor-I(IGF-I) exerts beneficial effects on cognitive function. Because stimulation of sensory neurons induces IGF-I production by releasing calcitonin gene-related peptide(CGRP) in the mouse brain, we hypothesized that donepezil may have a stimulatory effect on sensory neurons in addition to an inhibitory effect on acetylcholinesterase, thereby promoting angiogesis and neurogenesis through an increase in IGF-I production in the hippocampus. To examine this possibility, we analyzed the effects of two selective acetylcholinesterase inhibitors(donepezil and tacrine) on hippocampal IGF-I production and cognitive function in WT mice, CGRP-knockout[CGRP(-/-)] mice, and WT mice with functional sensory denervation caused by neonatal administration of capsaicin.