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在尸检和生物学研究中报告精神疾病特征。

Reporting Psychiatric Disease Characteristics in Post-Mortem- and Biological Research.

作者信息

Scheepstra Karel, Mizee Mark, Wever Dennis, Hsiao Cheng-Chih, Zhang Lin, Swaab Dick, Hamann Jörg, Huitinga Inge

机构信息

Neuroimmunology research group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.

Psychiatric Program of the Netherlands Brain Bank, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.

出版信息

Neurosci Insights. 2024 May 11;19:26331055241252632. doi: 10.1177/26331055241252632. eCollection 2024.

DOI:10.1177/26331055241252632
PMID:38737296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11088795/
Abstract

Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 ("don't eat me signals") located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after "psychological autopsy") selected by an experienced clinician.

摘要

炎症是抑郁症神经生物学中的一个重要假说。在我们对慢性重度抑郁症(MDD)患者小胶质细胞的转录组分析研究中,我们揭示了一种仅在皮质灰质中发现的独特的疾病相关小胶质细胞(DAM)转录组谱,我们将其命名为DepDAM。这些DepDAM显示出一种免疫抑制状态,通过上调位于突触上的CD200和CD47(“别吃我信号”),可能存在小胶质细胞抑制的上游机制。我们广泛报告了疾病特征,如死因、安乐死原因以及死亡时的精神状态。当排除处于心境正常状态的MDD供体时,白质小胶质细胞上CD45膜表达降低的趋势变得显著,灰质小胶质细胞的差异也变得更大。对于CD47和CD200的蛋白质印迹分析,明确抑郁的供体组(MDD-D)的平均值均升高。这强调了在尸检和生物精神病学研究中报告患者和发作特征的极端重要性,如严重程度、发作特征、自杀倾向(类型)、死亡方式以及死亡时的疾病状态。对于精神病学尸检研究,我们建议使用由经验丰富的临床医生挑选的特征明确的供体(例如,经过“心理尸检”)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa8/11088795/b1810dd30d0e/10.1177_26331055241252632-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa8/11088795/b1810dd30d0e/10.1177_26331055241252632-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa8/11088795/b1810dd30d0e/10.1177_26331055241252632-fig1.jpg

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Biol Psychiatry. 2023 Oct 15;94(8):619-629. doi: 10.1016/j.biopsych.2023.04.020. Epub 2023 Apr 28.
3
Microglia states and nomenclature: A field at its crossroads.
小胶质细胞状态和命名:一个处于十字路口的领域。
Neuron. 2022 Nov 2;110(21):3458-3483. doi: 10.1016/j.neuron.2022.10.020.
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Imaging the effect of ketamine on synaptic density (SV2A) in the living brain.在活体大脑中成像氯胺酮对突触密度(SV2A)的影响。
Mol Psychiatry. 2022 Apr;27(4):2273-2281. doi: 10.1038/s41380-022-01465-2. Epub 2022 Feb 15.
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Microglia and their LAG3 checkpoint underlie the antidepressant and neurogenesis-enhancing effects of electroconvulsive stimulation.小胶质细胞及其LAG3检查点是电休克治疗抗抑郁和促进神经发生作用的基础。
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