布罗德曼第 46 区的基因表达变化可区分精神分裂症和情绪障碍中表皮生长因子与免疫系统的相互作用。

IF 3 Q2 PSYCHIATRY
Tharini Ketharanathan, Avril Pereira, Suresh Sundram
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引用次数: 0

摘要

生命早期与压力和免疫相关的环境因素如何增加精神分裂症的风险易感性仍是一个未知数。我们研究了促炎症变化是否会扰乱大脑表皮生长因子(EGF)系统,该系统对神经发育和成熟的中枢神经系统功能(包括突触可塑性)至关重要。我们量化了精神分裂症患者、情绪障碍患者和神经典型对照组死后背外侧前额叶(DLPFC;布罗德曼区(BA)46)和眶额叶(OFC;BA11)皮层中关键 EGF 和免疫系统通路基因的 mRNA 水平和八种免疫蛋白。在 BA46 中,有 64 个基因的表达出现差异,主要是在精神分裂症患者中,其中 MAPK-ERK、NRG1-PI3K-AKT 和 mTOR 级联的表达减弱,表明 EGF 系统信号减少,免疫分子的表达也同样减弱,特别是在 TLR、TNF 和补体通路中,同时还发现 NF-κB1 蛋白水平降低,IL12RB2 蛋白水平升高。有证据表明,精神分裂症患者 BA46 中 ErbB-PI3K-AKT-mTOR 和 TLR 通路的汇聚发生了改变。BA11的变化相对较小。总体而言,不同通路基因表达的变化可能反映了精神分裂症和心境障碍之间涉及免疫和表皮生长因子系统信号的不同病理过程,尤其是在DLPFC中。此外,先天性免疫信号和候选 EGF 信号通路之间的异常趋同可能表明,在发育中的大脑中,在应对环境压力因素时存在着重要的病理相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Gene expression changes in Brodmann's Area 46 differentiate epidermal growth factor and immune system interactions in schizophrenia and mood disorders.

Gene expression changes in Brodmann's Area 46 differentiate epidermal growth factor and immune system interactions in schizophrenia and mood disorders.

How early in life stress-immune related environmental factors increase risk predisposition to schizophrenia remains unknown. We examined if pro-inflammatory changes perturb the brain epidermal growth factor (EGF) system, a system critical for neurodevelopment and mature CNS functions including synaptic plasticity. We quantified genes from key EGF and immune system pathways for mRNA levels and eight immune proteins in post-mortem dorsolateral prefrontal (DLPFC; Brodmann's Area (BA) 46) and orbitofrontal (OFC; BA11) cortices from people with schizophrenia, mood disorders and neurotypical controls. In BA46, 64 genes were differentially expressed, predominantly in schizophrenia, where attenuated expression of the MAPK-ERK, NRG1-PI3K-AKT and mTOR cascades indicated reduced EGF system signalling, and similarly diminished immune molecular expression, notably in TLR, TNF and complement pathways, along with low NF-κB1 and elevated IL12RB2 protein levels were noted. There was nominal evidence for altered convergence between ErbB-PI3K-AKT-mTOR and TLR pathways in BA46 in schizophrenia. Comparatively minimal changes were noted in BA11. Overall, distinct pathway gene expression changes may reflect variant pathological processes involving immune and EGF system signalling between schizophrenia and mood disorder, particularly in DLPFC. Further, the abnormal convergence between innate immune signalling and candidate EGF signalling pathways may indicate a pathologically important interaction in the developing brain in response to environmental stressors.

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