Running exercise- and antidepressant-induced increases in growth and survival-associated signaling molecules are IGF-dependent
Running exercise- and antidepressant-induced increases in growth and survival-associated signaling molecules are IGF-dependent
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DOI：
10.1080/08977190701602329
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发表时间：
2007-01-01
期刊：
影响因子：
1.8
通讯作者：
Russo-Neustadt, Amelia A.
中科院分区：
文献类型：
--
作者：
Chen, Michael J.;Russo-Neustadt, Amelia A.
众所周知，体育锻炼会增加海马脑源性神经营养因子 (BDNF) mRNA 和蛋白质，以及几种促生存信号蛋白的表达，其中许多影响取决于中枢神经系统对外周胰岛素样生长因子 - 1 (IGF-1) 的摄取。由于抗抑郁药治疗对神经营养蛋白表达具有类似的影响，因此我们研究了抗抑郁药诱导的 BDNF 变化是否也依赖于 IGF-1 的摄取，以及 IGF-1 是否在运动/抗抑郁药诱导的可塑性/生长相关分子（GAP-43、SCG-10）表达以及与神经元存活相关分子（Akt、ERK1/2）的细胞内激活中发挥作用。我们评估了一种著名的单胺氧化酶抑制剂反苯环丙明对 BDNF mRNA 和蛋白质水平以及磷酸化 Akt 和磷酸化 ERK1/2 免疫反应性的影响，无论是否通过使用针对 IGF-1 的抗血清系统性阻断 IGF-1 摄取。抗 IGF-1 可以逆转运动以及反苯环丙胺引起的 BDNF mRNA 和蛋白质的增加。运动还显着增强了轴突生长蛋白 GAP-43 的转录，这种作用也被证明是 IGF-1 依赖性的。运动加反苯环丙明的组合也增加了多种细胞存活信号测量，但与组合治疗相关的 BDNF 变化似乎与 IGF-1 的摄取无关。总之，这些结果表明，CNS 中外周 IGF-1 的摄取对于抗抑郁药物以及运动诱导的海马 BDNF 表达增强至关重要，从而增强海马神经元的存活和可塑性。
It is known that physical exercise increases hippocampal brain-derived neurotrophic factor ( BDNF) mRNA and protein, as well as the expression of several pro-survival signaling proteins and that many of these effects depend on the uptake of peripheral insulin-like growth factor-1 (IGF-1) into the CNS. Because treatment with antidepressants has similar effects upon neurotrophin expression, we investigated whether antidepressant-induced BDNF changes also depend on IGF-1 uptake, as well as whether IGF-1 plays a role in the exercise/antidepressant-induced expression of molecules associated with plasticity/growth (GAP-43, SCG-10) and the intracellular activation of molecules associated with neuronal survival (Akt, ERK1/2). We evaluated the effects of a well known monoamine oxidase inhibitor, tranylcypromine, on BDNF mRNA and protein levels and phospho-Akt and phospho-ERK1/2 immunoreactivity, both with and without systemic blockade of IGF-1 uptake through the use of an antiserum raised against IGF-1. Anti-IGF-1 reversed the increase in BDNF mRNA and protein elicited by exercise as well as tranylcypromine. Exercise also significantly enhanced transcription of axon growth protein, GAP-43, an effect that was also evidenced to be IGF-1-dependent. The combination of exercise-plus-tranylcypromine also increased several cell survival signaling measures, but the BDNF changes associated with the combination treatment appeared to be independent of IGF-1 uptake. Together, these results indicate that the uptake of peripheral IGF-1 in the CNS is essential for antidepressant- as well as exercise-induced enhancement in hippocampal BDNF expression and thus, enhanced hippocampal neuronal survival and plasticity.