Kappa opioid receptors in rat spinal cord: Sex-linked distribution differences
Kappa opioid receptors in rat spinal cord: Sex-linked distribution differences
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DOI：
10.1016/j.neuroscience.2003.12.042
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Drake, CT
中科院分区：
文献类型：
--
作者：
Harris, JA;Chang, PC;Drake, CT
激活脊髓中的K阿片受体(Kors)可以减少伤害性感受。人类和啮齿动物在KOR激动剂产生的止痛方面表现出性别差异，雌性大鼠在整个发情周期中KOR密度和敏感度出现波动。然而，目前尚不清楚脊髓KOR的数量和/或分布是否存在性别差异。本研究用免疫细胞化学方法观察了正常骑行的雌性SD大鼠和雄性SD大鼠腰骶段脊髓背角I层和11层的KRs免疫细胞化学标记。用定性电子显微镜(EM)确定KOR标记的基本模式，用定量电子显微镜和光学显微镜确定KOR免疫反应密度和亚细胞分布的性别差异。KOR标记用免疫过氧化物酶进行可视化，以获得最佳的灵敏检测，或用免疫金进行精确的亚细胞定位。EM显示，男性和女性KOR免疫反应的一般模式相似。KOR免疫反应主要见于树突、轴突和轴突终末，少数胶质细胞和神经元胞体内有KOR免疫反应。KOR免疫反应阳性的轴突多为细小的无髓轴突。KOR-ir终末多为中小型，少数与未标记的树突形成不对称或对称突触。KOR免疫反应与细胞膜和胞浆细胞器有关，特别是终末有致密的核心小泡。光镜下，KOR免疫反应阳性细胞在动情期和动情期女性明显高于男性。在EM中，KOR免疫金标记物在轴突终末的分布有所不同，动情期女性比男性胞浆KOR标记的比例更大。相比之下，KOR免疫过氧化物酶标记的图谱的丰度和类型并没有显示出性别关联的差异。我们的结论是，在两性中，Kors既影响突触前和突触后的神经传递，也存在于形态不同的神经元群体中。这些发现与脊髓KOR激活的复杂后果是一致的。此外，发情前期/发情期女性的KOR密度增加和细胞内KOR比例增加的存在表明KOR介导的抗伤害感受存在性别相关的差异。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
AActivation Of K opioid receptors (KORs) in the spinal cord can diminish nociception. Humans and rodents show sex differences in the analgesia produced by KOR agonists, and female rats show fluctuations in KOR density and sensitivity across the estrous cycle. However, it is unclear whether there are sex differences in the amount and/or distribution of spinal KORs. In the present study, immunocytochemically labeled KORs were examined in laminae I and 11 of the lumbosacral spinal dorsal horn of male and normally cycling female Sprague-Dawley rats. The basic pattern of KOR labeling was determined in both sexes using qualitative electron microscopy (EM), and sex-linked differences in the density and subcellular distribution of KOR immunoreactivity were determined with quantitative EM and light microscopy. KOR labeling was visualized with immunoperoxidase for optimally sensitive detection, or with immunogold for precise subcellular localization. By EM, the general pattern of KOR immunoreactivity was similar in males and females. KOR immunoreactivity was common in dendrites, axons, and axon terminals, and was in a few glia and neuronal somata. Most KOR-immunoreactive (4) axons were fine-diameter and unmyelinated. Most KOR-ir terminals were small or mediumsized, and a minority formed asymmetric or symmetric synapses with unlabeled dendrites. KOR immunoreactivity was associated both with the plasma membrane and with cytoplasmic organelles, notably including dense core vesicles in terminals. Light microscopic densitometry revealed that KOR immunoreactivity was significantly denser in estrus and proestrus females than in males. By EM, the distribution of KOR-immunogold labeling within axon terminals differed, with a greater proportion of cytoplasmic KOR labeling in estrus females compared with males. In contrast, the abundance and types of KOR-immunoperoxidase-labeled profiles did not show sex-linked differences. We conclude that in both sexes, KORs are positioned to influence both pre- and postsynaptic neurotransmission and are present in morphologically heterogeneous neuron populations. These findings are consistent with complex consequences of KOR activation in the spinal cord. In addition, the presence of increased KOR density and proportionally elevated intracellular KORs in proestrus/estrus females suggests a basis for sex-linked differences in KOR-mediated antinociception. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.