锌信号通过 PAF 受体途径控制星形胶质细胞依赖性突触调节。

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Janelle E Stanton, Sakshi Hans, Ioannis Zabetakis, Andreas M Grabrucker
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引用次数: 0

摘要

星形胶质细胞是神经元发育和活动的重要调节器。星形胶质细胞的活化在应对许多中枢神经系统(CNS)病症中起着关键作用。然而,反应性星形胶质细胞是一把双刃剑,因为它们的长期或过度激活可能会对中枢神经系统的生理学产生负面影响,例如通过对突触生成和突触功能的异常调节。因此,星形胶质细胞的激活与神经退行性疾病和神经发育障碍有关。因此,抑制星形胶质细胞的活化可能是预防和治疗这些疾病的重要方法。由于锌缺乏一直与促炎症信号传导增加有关,我们旨在利用免疫细胞化学和蛋白质生物化学检测星形胶质细胞 GFAP 表达、荧光成像检测活化星形胶质细胞中的氧化应激水平、细胞因子谱分析以及星形胶质细胞分泌物对原代神经元的分析等技术,确定可能导致星形胶质细胞活化的细胞锌依赖信号传导途径。我们的研究结果揭示了星形胶质细胞中一个迄今为止尚未被充分描述的通路--血小板活化因子受体(PAFR)通路,它是一个关键的锌依赖信号通路,足以控制星形胶质细胞的反应性。低锌水平会激活 PAFR 信号驱动的星形胶质细胞与神经元之间的串扰,从而以 PAFR 依赖性的方式改变发育过程中兴奋性突触的形成。我们的结论是,锌是参与星形胶质细胞活化的关键信号离子,也是控制星形胶质细胞促炎过程的重要饮食因子。因此,针对锌的平衡可能是治疗多种神经炎症的重要方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Zinc signaling controls astrocyte-dependent synapse modulation via the PAF receptor pathway.

Astrocytes are important regulators of neuronal development and activity. Their activation plays a key role in the response to many central nervous system (CNS) pathologies. However, reactive astrocytes are a double-edged sword as their chronic or excessive activation may negatively impact CNS physiology, for example, via abnormal modulation of synaptogenesis and synapse function. Accordingly, astrocyte activation has been linked to neurodegenerative and neurodevelopmental disorders. Therefore, the attenuation of astrocyte activation may be an important approach for preventing and treating these disorders. Since zinc deficiency has been consistently linked to increased pro-inflammatory signaling, we aimed to identify cellular zinc-dependent signaling pathways that may lead to astrocyte activation using techniques such as immunocytochemistry and protein biochemistry to detect astrocyte GFAP expression, fluorescent imaging to detect oxidative stress levels in activated astrocytes, cytokine profiling, and analysis of primary neurons subjected to astrocyte secretomes. Our results reveal a so far not well-described pathway in astrocytes, the platelet activation factor receptor (PAFR) pathway, as a critical zinc-dependent signaling pathway that is sufficient to control astrocyte reactivity. Low zinc levels activate PAFR signaling-driven crosstalk between astrocytes and neurons, which alters excitatory synapse formation during development in a PAFR-dependent manner. We conclude that zinc is a crucial signaling ion involved in astrocyte activation and an important dietary factor that controls astrocytic pro-inflammatory processes. Thus, targeting zinc homeostasis may be an important approach in several neuroinflammatory conditions.

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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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