Department of Medicine, University of California Medical Center, San Francisco, CA, USA.
Department of Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, CT, USA.
Transl Psychiatry. 2020 Oct 26;10(1):361. doi: 10.1038/s41398-020-01046-3.
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.
评估了急性精神病患者中涉及脑创伤和退行性疾病的潜在神经毒性系统。从未经治疗的首发精神病患者（FPs）和十名匹配的正常对照者（Cs）的血浆中免疫沉淀提取星形胶质细胞衍生的外体（ADEs）和神经元衍生的外体（NDEs）。用 ELISA 提取、定量并标准化神经线粒体电子传递和补体蛋白，与 CD81 外体标志物的水平进行比较。NADH-泛醌氧化还原酶（复合物 I）的亚基 1 和 6 和细胞色素 b-c1 氧化酶（复合物 III）的亚基 10 的水平，但细胞色素 C 氧化酶（复合物 IV）的亚基 1 或超氧化物歧化酶 1（SOD1）的水平在 FPs 的 ADEs 和 NDEs 中明显低于 Cs。这种电子传递蛋白的失调模式与活性氧的产生增加有关。FPs 的 ADE 神经胶质纤维酸性蛋白水平明显高于 Cs，表明 FPs 中炎症星形胶质细胞的比例更高。FPs 的 ADE 补体蛋白 C3b 调理素水平明显升高，C5b-9 攻击复合物水平略有升高。FPs 的 ADE 补体 C3 转化酶抑制剂 CD55 水平明显降低，可能解释了 C3 转化酶生成的 C3b 水平升高。FPs 的 ADE 白血病抑制因子（LIF）水平明显低于 Cs，而白细胞介素 6（IL-6）水平则没有差异。血浆神经外体电子传递和补体蛋白水平可能有助于预测 FP 并指导治疗。SOD 模拟物、C3 转化酶抑制剂和 LIF 受体激动剂也可能对 FP 具有治疗益处。
