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孕期长期使用吗啡会改变出生后小鼠大脑中钙结合蛋白D-28k的表达模式。

Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain.

作者信息

Mithbaokar Pratibha, Fiorito Filomena, Della Morte Rossella, Maharajan Veeramani, Costagliola Anna

机构信息

Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, via F. Delpino, 1, Naples, 80137, Italy.

Department of Chemistry, Istituto Zooprofilattico Sperimentale Del Mezzogiorno, via Salute, 2, Portici, Naples, 80055, Italy.

出版信息

Synapse. 2016 Jan;70(1):15-23. doi: 10.1002/syn.21866. Epub 2015 Oct 16.

Abstract

The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain.

摘要

在慢性吗啡暴露的成年小鼠的几个脑区中,表达钙结合蛋白(CB)-D28k的神经元的分布模式发生了改变。在本研究中,调查了母体慢性暴露于吗啡对小鼠后代大脑中表达CB-D28k的神经元分布模式的影响。在交配前、整个妊娠期以及产后21天,对CD-1小鼠雌性每天给予生理盐水或吗啡,持续7天。在出生后第18天处死它们的后代,并用甲酚紫进行组织学检查,并用兔多克隆抗CB-D28k抗体进行免疫组织化学检查。组织学检查显示,对照组小鼠后代前脑与两组不同剂量吗啡处理的小鼠后代前脑在神经元分布模式和数量上没有显著差异。然而,免疫组织化学分析显示,在扣带回皮质、顶叶皮质II-IV层以及海马体的所有区域,CB-D28k免疫反应性神经元的数量显著减少,而在顶叶皮质V-VI层和吗啡处理小鼠后代大脑的下托区域,其数量增加。总体而言,我们的研究结果表明,母体暴露于吗啡会以层和剂量依赖的方式改变小鼠发育大脑特定区域中CB-D28k表达神经元的模式,从而表明这些改变可能代表了吗啡改变发育中大脑功能方面的一种机制。

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