摘要
在这项研究中,一个二维凝胶蛋白组学方法被应用于概括潜在于中风后抑郁症(PSD)的重大不良反应中的蛋白改变。鉴于左前额皮质功能障碍和PSD之间的紧密联系,通过慢性轻度应激(CMS)3周后左前额皮质损伤建立PSD鼠模型。通过蔗糖偏好测试,PSD鼠在CMS全程显示了类似抑郁行为。相比之下,中风鼠在中风后第一周显示了类似抑郁行为,在中风后第二周恢复。为探讨PSD-诱导的蛋白表达变化,对中风、PSD和对照组鼠的同侧海马蛋白表达进行了比较分析。确定了46个不同蛋白,其中22个蛋白通过中风和中风后应激被调节到反方向。这些22个蛋白中的大部分与神经产生、细胞骨架改变和能量代谢有关。其他的蛋白与线粒体抗氧化应激系统功能相关。经中风和中风后应激的反向蛋白表达可能在成年大脑损伤后自我修复中发挥作用,显示了在鼠海马中,中风诱导自我修复机制,而中风后应激使自我修复机制减轻。在反向不同蛋白特异表达中,3个参与线粒体抗氧化应激的线粒体蛋白:热休克70 kDa 蛋白 9,氧化物酶-6和抗增殖蛋白得到验证,并可能在中风损伤自我修复和PSD诱导的海马神经元的损伤中发挥作用。 这些发现为解释在中风恢复中支撑PSD不良反应的分子机制提供了新见解。
关键词: 海马体,线粒体抗氧化应激,中风后抑郁,蛋白质组学,中风
Current Molecular Medicine
Title:Ipsilateral Hippocampal Proteomics Reveals Mitochondrial Antioxidative Stress Impairment in Cortical-Lesioned Chronic Mild Stressed Rats
Volume: 14 Issue: 9
Author(s): J. Pan, H. Liu, J. Zhou, Z. Liu, Y. Yang, Y. Peng, H. You, D. Yang and P. Xie
Affiliation:
关键词: 海马体,线粒体抗氧化应激,中风后抑郁,蛋白质组学,中风
摘要: In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a left anterior cortical lesion followed by chronic mild stress (CMS) for three weeks. Through sucrose preference testing, PSD rats displayed depression-like behavior during the entire CMS period. In contrast, stroke rats displayed depression-like behavior in the first week post-stroke and recovered in the second week post-stroke. To investigate the PSD-induced protein expression changes, ipsilateral hippocampal protein expression in stroke, PSD, and control rats were comparatively analyzed. 46 differential proteins were identified, 22 of which were regulated in opposing directions by stroke and post-stroke stress. The majority of these 22 proteins were involved in neurogenesis, cytoskeletal remodeling, and energy metabolism. Additional proteins were functionally related to mitochondrial antioxidative stress systems. The differential proteins expressed in opposing directions by stroke and post-stroke stress may play a role in self-repair after adult brain lesions, suggesting that stroke induces self-repair mechanisms, while post-stoke stress mitigates them, in the rat hippocampus. Among these differential proteins dysregulated in opposing directions, three mitochondrial proteins involved in mitochondrial antioxidative stress – heat shock 70 kDa protein 9, peroxiredoxin-6, and prohibitin – were validated and may play an important role in stroke-injury self-repair and PSD-induced injury of hippocampal neurons. These findings offer new insight into deciphering the molecular mechanisms underpinning PSD's adverse effects on stroke recovery.
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Pan J., Liu H., Zhou J., Liu Z., Yang Y., Peng Y., You H., Yang D. and Xie P., Ipsilateral Hippocampal Proteomics Reveals Mitochondrial Antioxidative Stress Impairment in Cortical-Lesioned Chronic Mild Stressed Rats, Current Molecular Medicine 2014; 14 (9) . https://dx.doi.org/10.2174/1566524014666141021143333
DOI https://dx.doi.org/10.2174/1566524014666141021143333 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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