Autophagy Inhibition in Endogenous and Nutrient-Deprived Conditions Reduces Dorsal Root Ganglia Neuron Survival and Neurite Growth In Vitro
Autophagy Inhibition in Endogenous and Nutrient-Deprived Conditions Reduces Dorsal Root Ganglia Neuron Survival and Neurite Growth In Vitro
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DOI：
10.1002/jnr.23733
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发表时间：
2016-07-01
影响因子：
4.2
通讯作者：
Mearow, Karen
中科院分区：
文献类型：
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作者：
Clarke, Joseph-Patrick;Mearow, Karen
周围神经病变可导致轴突中的细胞骨架变化，最终导致沃勒变性和细胞死亡。最近，自噬被研究为改善周围神经损伤期间轴突存活和生长的潜在靶点。本研究探讨了在控制和营养剥夺条件下，自噬对成人背根神经节（DRG）神经元存活和轴突生长的影响。用药理学活化剂（雷帕霉素; Rapa）和抑制剂（3-甲基腺嘌呤，巴弗洛霉素A1）结合营养稳定的环境（标准培养基）或营养缺乏的环境（Hank平衡盐溶液+Ca 2 +/Mg 2+）调节组成性自噬。结果表明，自噬抑制降低了细胞活力，减少了轴突生长和分支的复杂性。尽管与对照组相比，营养剥夺上调了自噬，但雷帕霉素没有进一步激活自噬，表明自噬存在阈值水平。总的来说，细胞和生物化学方法相结合，显示自噬对成年DRG神经元存活和生长的影响。(C)2016 Wiley Periodicals，Inc.
Peripheral neuropathies can result in cytoskeletal changes in axons, ultimately leading to Wallerian degeneration and cell death. Recently, autophagy has been studied as a potential target for improving axonal survival and growth during peripheral nerve damage. This study investigates the influence of autophagy on adult dorsal root ganglia (DRG) neuron survival and axonal growth under control and nutrient deprivation conditions. Constitutive autophagy was modulated with pharmacological activators (rapamycin; Rapa) and inhibitors (3-methyladenine, bafilomycin A1) in conjunction with either a nutrient-stable environment (standard culture medium) or a nutrient-deprived environment (Hank's balanced salt solution + Ca2+/Mg2+). The results demonstrated that autophagy inhibition decreased cell viability and reduced neurite growth and branching complexity. Although autophagy was upregulated with nutrient deprivation compared with the control, it was not further activated by rapamycin, suggesting a threshold level of autophagy. Overall, both cellular and biochemical approaches combined to show the influence of autophagy on adult DRG neuron survival and growth. (C) 2016 Wiley Periodicals, Inc.