Regulation of morphine-induced synaptic alterations: Role of oxidative stress, ER stress, and autophagy.
Regulation of morphine-induced synaptic alterations: Role of oxidative stress, ER stress, and autophagy.
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DOI：
10.1083/jcb.201605065
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发表时间：
2016-10-24
期刊：
影响因子：
--
通讯作者：
Buch S
中科院分区：
文献类型：
--
作者：
Cai Y;Yang L;Hu G;Chen X;Niu F;Yuan L;Liu H;Xiong H;Arikkath J;Buch S
蔡等人。证明吗啡暴露会失调海马突触平衡。这种效应涉及一种涉及 ROS、ER 应激和自噬的新途径，并且可以通过 PDGF 来挽救。我们的研究结果表明，吗啡通过涉及活性氧（ROS）、内质网（ER）应激和自噬的新型信号通路，使海马体（学习和记忆的关键中心）的突触平衡失调。我们在这项研究中证明，海马神经元暴露吗啡会导致兴奋性突触密度降低，同时通过激活μ阿片受体而增强抑制性突触密度。此外，吗啡的这些作用是通过 NADPH 氧化酶上调细胞内 ROS 介导的，进而导致 ER 应激和自噬的连续诱导。吗啡对突触密度的有害影响被证明可以被血小板衍生生长因子（PDGF）逆转，PDGF 是一种与神经保护有关的多效性生长因子。这些结果确定了一种涉及吗啡介导的突触改变的新细胞机制，对 PDGF 的治疗干预具有重要意义。
Cai et al. demonstrate that morphine exposure dysregulates synaptic balance in the hippocampus. This effect involves a novel pathway involving ROS, ER stress, and autophagy and can be rescued by PDGF. Our findings suggest that morphine dysregulates synaptic balance in the hippocampus, a key center for learning and memory, via a novel signaling pathway involving reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy. We demonstrate in this study that exposure of morphine to hippocampal neurons leads to a reduction in excitatory synapse densities with a concomitant enhancement of inhibitory synapse densities via activation of the μ opioid receptor. Furthermore, these effects of morphine are mediated by up-regulation of intracellular ROS from NADPH oxidase, leading, in turn, to sequential induction of ER stress and autophagy. The detrimental effects of morphine on synaptic densities were shown to be reversed by platelet-derived growth factor (PDGF), a pleiotropic growth factor that has been implicated in neuroprotection. These results identify a novel cellular mechanism involved in morphine-mediated synaptic alterations with implications for therapeutic interventions by PDGF.
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