MORPHINE INHIBITS PURKINJE-CELL SURVIVAL AND DENDRITIC DIFFERENTIATION IN ORGANOTYPIC CULTURES OF THE MOUSE CEREBELLUM
MORPHINE INHIBITS PURKINJE-CELL SURVIVAL AND DENDRITIC DIFFERENTIATION IN ORGANOTYPIC CULTURES OF THE MOUSE CEREBELLUM
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DOI：
10.1006/exnr.1994.1188
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发表时间：
1994-11-01
影响因子：
5.3
通讯作者：
TURBEK, CS
中科院分区：
文献类型：
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作者：
HAUSER, KF;GURWELL, JA;TURBEK, CS
本实验观察了吗啡对1日龄或7日龄小鼠小脑组织块培养的钙结合蛋白-D-28 k免疫反应浦肯野细胞的形态发生和存活的影响。为了减少实验的变异性，双边匹配的器官型培养对用于比较阿片类药物治疗的效果。每对中的一个外植体未处理，而剩余的外植体用吗啡、吗啡加纳洛酮或仅纳洛酮连续处理7至10天。在来自1日龄小鼠的外植体中，与对称匹配的未处理对照外植体相比，吗啡处理显著降低了浦肯野细胞树突长度。估计导致树突长度半数最大减少（EC（50））的吗啡浓度为4.9 × 10（-8）M。在较高浓度（EC（50）= 3.6 × 10（-6）M），吗啡也显着减少浦肯野细胞的数量在外植体从1日龄小鼠相比，未经处理的外植体。电子显微镜检查发现，在1日龄小鼠的外植体中，退化的浦肯野细胞数量增加。这表明高浓度（10（-5）M）的吗啡通过降低浦肯野细胞的存活率而减少了它们的数量。在来自7日龄小鼠的外植体中，与对称匹配的未处理（对照）外植体相比，吗啡（10（-5）M）既不影响浦肯野细胞树突长度，也不影响细胞数量。总的来说，这些研究结果表明，吗啡本身，通过对小脑的直接作用，可以影响浦肯野细胞的分化和生存。研究结果还表明，在发育过程中有一个关键时期，浦肯野细胞特别容易受到吗啡的影响。(C)1994年出版社出版。
The effects of morphine on the morphogenesis and survival of calbindin-D-28k-immunoreactive Purkinje cells were studied in organotypic explant cultures isolated from 1- or 7-day-old mouse cerebella. To reduce experimental variability, bilaterally matched pairs of organotypic cultures were used to compare the effects of opiate drug treatment. One explant within each pair was untreated, while the remaining explant was continuously treated for 7 to 10 days with morphine, morphine plus naloxone, or naloxone alone. In explants derived from 1-day-old mice, morphine treatment significantly reduced Purkinje cell dendritic length compared to symmetrically matched untreated control explants. The concentration of morphine estimated to cause a half-maximal reduction (EC(50)) in dendritic length was 4.9 x 10(-8) M. At higher concentrations (EC(50) = 3.6 X 10(-6) M), morphine also significantly decreased the number of Purkinje cells in explants from 1-day-old mice compared to untreated explants. Electron microscopy identified increased numbers of degenerating Purkinje cells in explants derived from 1-day-old mice. This showed that high concentrations (10(-5) M) of morphine reduced Purkinje cell numbers by decreasing their rate of survival. In explants derived from 7-day-old mice, morphine (10(-5) M) neither affected Purkinje cell dendritic length nor cell numbers compared to symmetrically matched untreated (control) explants. Collectively, these findings suggest that morphine per se, through a direct action on the cerebellum, can affect Purkinje cell differentiation and survival. The results additionally suggest that there is a critical period during development when Purkinje cells are especially vulnerable to the effects of morphine. (C) 1994 Academic Press, Inc.