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精神分裂症患者前额叶灰质中小胶质细胞与神经元的相互作用:一项死后超微结构形态计量学研究

Microglia-neuron interactions in prefrontal gray matter in schizophrenia: a postmortem ultrastructural morphometric study.

作者信息

Uranova N A, Vikhreva O V, Rakhmanova V I

机构信息

Laboratory of Clinical Neuropathology, Mental Health Research Center, Kashirskoe Shosse 34, 115522, Moscow, Russia.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2023 Dec;273(8):1633-1648. doi: 10.1007/s00406-023-01621-x. Epub 2023 May 13.

Abstract

This study addressed the question of whether the interaction between neurons and satellite microglia (SatMg) is abnormal in schizophrenia. SatMg-neuron communication at direct contacts between neuronal soma is essential for neuroplasticity as SatMg can regulate neuronal activity. A postmortem ultrastructural morphometric study was performed to investigate SatMg and adjacent neurons in layer 5 of the prefrontal cortex in 21 cases of schizophrenia and 20 healthy controls. Density of SatMg was significantly higher in the young schizophrenia group and in the group with illness duration ≤ 26 years as compared to controls. We found lower volume fraction (Vv) and the number (N) of mitochondria and higher Vv and N of lipofuscin granules and vacuoles in endoplasmic reticulum in SatMg in the schizophrenia compared to the control brain. These changes progressed with age and illness duration. A significantly higher soma area and Vv of vacuoles of endoplasmic reticulum were revealed in neurons in schizophrenia as compared to controls. Negative significant correlations between N of vacuoles in neurons and N of mitochondria in SatMg were found in the control group but not in the schizophrenia group. Area of vacuole in neurons was significantly positively correlated with Vv and area of mitochondria in SatMg in the control group and negatively in the schizophrenia group. Correlation coefficients between these parameters differed significantly between the groups. These results indicate disturbed SatMg-neuron interactions in the schizophrenia brain and suggest a key role of mitochondrial abnormalities in SatMg in these disturbances.

摘要

本研究探讨了精神分裂症患者神经元与卫星小胶质细胞(SatMg)之间的相互作用是否异常。由于SatMg可调节神经元活动,因此神经元胞体直接接触处的SatMg-神经元通讯对于神经可塑性至关重要。进行了一项死后超微结构形态计量学研究,以调查21例精神分裂症患者和20名健康对照者前额叶皮质第5层中的SatMg和相邻神经元。与对照组相比,年轻精神分裂症组和病程≤26年的组中SatMg的密度显著更高。我们发现,与对照脑相比,精神分裂症患者SatMg中线粒体的体积分数(Vv)和数量(N)更低,而内质网中脂褐素颗粒和液泡的Vv和N更高。这些变化随着年龄和病程的增加而进展。与对照组相比,精神分裂症患者神经元的胞体面积和内质网液泡的Vv显著更高。在对照组中发现神经元液泡的N与SatMg中线粒体的N呈显著负相关,而在精神分裂症组中未发现。在对照组中,神经元液泡的面积与SatMg中线粒体的Vv和面积呈显著正相关,而在精神分裂症组中呈负相关。这些参数之间的相关系数在两组之间存在显著差异。这些结果表明精神分裂症患者大脑中SatMg-神经元相互作用受到干扰,并提示SatMg中线粒体异常在这些干扰中起关键作用。

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