Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis.
Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis.
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线粒体电子转运蛋白的降低，并增加了早期精神病血浆神经源性外泌体中补体介质。
DOI：
10.1038/s41398-020-01046-3
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发表时间：
2020-10-26
影响因子：
6.8
通讯作者：
Heninger GR
中科院分区：
文献类型：
--
作者：
Goetzl EJ;Srihari VH;Guloksuz S;Ferrara M;Tek C;Heninger GR
在急性精神病中评估了与脑创伤和退行性疾病有关的潜在神经毒性系统。用免疫沉淀法从10例首发精神病患者(FP)和10例正常对照(Cs)的血浆中分离出星形胶质细胞来源的外切体(ADE)和神经元来源的外切体(NDE)。提取神经线粒体电子传递蛋白和补体蛋白，用ELISAs定量，并用CD81外切体标记水平归一化。FPS的ADE和NDE的NADH-泛醌氧化还原酶(复合体I)亚基1、6和细胞色素b-C1氧化酶亚基10(复合体III)的水平显著低于Cs，而细胞色素C氧化酶亚基1(复合体IV)和超氧化物歧化酶1(SOD 1)的亚基水平不显著低于Cs。这种电子传递蛋白的失调模式与活性氧物种的生成增加有关。FP组ADE胶质纤维酸性蛋白水平显著高于Cs组，提示FP组炎性星形胶质细胞所占比例较高。FPS患者的补体C3b调理素水平显著高于对照组，C5b-9攻击复合体水平略高于对照组。C3转换酶抑制剂CD55的ADE水平显著降低，可能解释了C3转换酶产生的C3b水平较高的原因。FFP组神经保护蛋白白血病抑制因子(LIF)水平显著低于Cs组，而IL-6水平无明显差异。血浆神经外切体电子传递和补体蛋白水平可能有助于预测FP和指导治疗。超氧化物歧化酶模拟物、C3转换酶抑制剂和LIF受体激动剂也可能对FP有治疗作用。
Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron transport and complement proteins were extracted, quantified by ELISAs and normalized with levels of CD81 exosome marker. Levels of subunits 1 and 6 of NADH-ubiquinone oxidoreductase (complex I) and subunit 10 of cytochrome b-c1 oxidase (complex III), but not of subunit 1 of cytochrome C oxidase (complex IV) or superoxide dismutase 1 (SOD1) were significantly lower in ADEs and NDEs of FPs than Cs. This dysregulated pattern of electron transport proteins is associated with increased generation of reactive oxygen species. ADE glial fibrillary acidic protein levels were significantly higher in FPs than Cs, indicating a higher percentage of inflammatory astrocytes in FPs. ADE levels of C3b opsonin were significantly higher and those of C5b-9 attack complex was marginally higher in FPs than Cs. A significantly lower ADE level of the C3 convertase inhibitor CD55 may explain the higher levels of C3 convertase-generated C3b. ADE levels of the neuroprotective protein leukemia inhibitory factor (LIF) were significantly lower in FPs than Cs, whereas levels of IL-6 were no different. Plasma neural exosome levels of electron transport and complement proteins may be useful in predicting FP and guiding therapy. SOD mimetics, C3 convertase inhibitors and LIF receptor agonists also may have therapeutic benefits in FP.
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影响因子：
5.3
作者：
Ben Haim L;Carrillo-de Sauvage MA;Ceyzériat K;Escartin C
通讯作者：
Escartin C
影响因子：
13.5
作者：
Davis SM;Pennypacker KR
通讯作者：
Pennypacker KR
影响因子：
6.1
作者：
Selfridge, J. Eva;E, Lezi;Lu, Jianghua;Swerdlow, Russell H.
通讯作者：
Swerdlow, Russell H.
DOI：
10.1159/000484348
发表时间：
2018-02-01
期刊：
Molecular neuropsychiatry
影响因子：
--
作者：
Rollins, Brandi L;Morgan, Ling;Vawter, Marquis P
通讯作者：
Vawter, Marquis P
DOI：
10.1016/j.dadm.2018.11.002
发表时间：
2019-12-01
影响因子：
5.3
作者：
Winston, Charisse N.;Goetzl, Edward J.;Rissman, Robert A.
通讯作者：
Rissman, Robert A.