Oligodendrocyte responses to buprenorphine uncover novel and opposing roles of μ-opioid- and nociceptin/orphanin FQ receptors in cell development: Implications for drug addiction treatment during pregnancy
Oligodendrocyte responses to buprenorphine uncover novel and opposing roles of μ-opioid- and nociceptin/orphanin FQ receptors in cell development: Implications for drug addiction treatment during pregnancy
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DOI：
10.1002/glia.21253
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发表时间：
2012-01-01
期刊：
影响因子：
6.2
通讯作者：
Sato-Bigbee, Carmen
中科院分区：
文献类型：
--
作者：
Eschenroeder, Andrew C.;Vestal-Laborde, Allison A.;Sato-Bigbee, Carmen
尽管髓磷脂的经典功能是促进跳跃式传导，但这种膜和少突胶质细胞（在中枢神经系统（CNS）中产生髓磷脂的细胞）现在被认为是发育中大脑可塑性和重塑的重要调节因子。因此，少突胶质细胞的成熟和髓鞘形成是中枢神经系统发育过程中最脆弱的过程之一。我们之前已经证明，丁丙诺啡会显着改变大鼠脑髓鞘形成，丁丙诺啡是一种阿片类似物，目前用于治疗怀孕阿片类药物成瘾者的临床试验。围产期暴露于低水平的该药物可诱导髓磷脂碱性蛋白 (MBP)、细胞和髓磷脂成分（成熟少突胶质细胞的标志物）表达加速和增加。相反，超治疗药物剂量会延迟 MBP 的脑表达，并导致有髓鞘轴突数量减少。我们现在发现，丁丙诺啡的这种双相剂量反应可归因于少突胶质细胞中μ阿片受体（MOR）和伤害感受素/孤啡肽FQ受体（NOP受体）的参与。这是特别有趣的，因为 NOP 受体/伤害感受素系统主要与行为和疼痛调节有关，但之前尚未描述过它在中枢神经系统发育或髓鞘形成中的作用。我们的研究结果表明，(a) MOR 激活和 (b) 包括 NOP 受体在内的一种新颖但尚未识别的途径介导的信号之间的平衡，在少突胶质细胞成熟和髓磷脂合成的时间中起着至关重要的作用。此外，接触阿片类药物可能会破坏这两个系统之间的正常相互作用，从而改变大脑髓鞘形成的发育模式。 (C) 2011 Wiley Periodicals, Inc.
Although the classical function of myelin is the facilitation of saltatory conduction, this membrane and the oligodendrocytes, the cells that make myelin in the central nervous system (CNS), are now recognized as important regulators of plasticity and remodeling in the developing brain. As such, oligodendrocyte maturation and myelination are among the most vulnerable processes along CNS development. We have shown previously that rat brain myelination is significantly altered by buprenorphine, an opioid analogue currently used in clinical trials for managing pregnant opioid addicts. Perinatal exposure to low levels of this drug induced accelerated and increased expression of myelin basic proteins (MBPs), cellular and myelin components that are markers of mature oligodendrocytes. In contrast, supra-therapeutic drug doses delayed MBP brain expression and resulted in a decreased number of myelinated axons. We have now found that this biphasic-dose response to buprenorphine can be attributed to the participation of both the mu-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOP receptor) in the oligodendrocytes. This is particularly intriguing because the NOP receptor/nociceptin system has been primarily linked to behavior and pain regulation, but a role in CNS development or myelination has not been described before. Our findings suggest that balance between signaling mediated by (a) MOR activation and (b) a novel, yet unidentified pathway that includes the NOP receptor, plays a crucial role in the timing of oligodendrocyte maturation and myelin synthesis. Moreover, exposure to opioids could disrupt the normal interplay between these two systems altering the developmental pattern of brain myelination. (C) 2011 Wiley Periodicals, Inc.