Pan J, Liu H, Zhou J, Liu Z, Yang Y, Peng Y, You H, Yang D, Xie P
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Yongchuan District, Chongqing 402460, China.
Curr Mol Med. 2014;14(9):1186-96. doi: 10.2174/1566524014666141021143333.
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.
在本研究中，采用二维凝胶蛋白质组学方法来剖析中风后抑郁症（PSD）显著不良影响背后的蛋白质变化。鉴于左前额叶皮质功能障碍与PSD之间的密切关联，通过左侧前皮质损伤并随后进行为期三周的慢性轻度应激（CMS）构建了PSD大鼠模型。通过蔗糖偏好测试，PSD大鼠在整个CMS期间表现出抑郁样行为。相比之下，中风大鼠在中风后第一周表现出抑郁样行为，并在中风后第二周恢复。为了研究PSD诱导的蛋白质表达变化，对中风、PSD和对照大鼠的同侧海马蛋白质表达进行了比较分析。鉴定出46种差异蛋白质，其中22种在中风和中风后应激下呈相反方向调节。这22种蛋白质中的大多数参与神经发生、细胞骨架重塑和能量代谢。其他蛋白质在功能上与线粒体抗氧化应激系统相关。中风和中风后应激以相反方向表达的差异蛋白质可能在成年脑损伤后的自我修复中起作用，这表明中风诱导自我修复机制，而中风后应激则减轻这些机制，在大鼠海马中。在这些以相反方向失调的差异蛋白质中，验证了三种参与线粒体抗氧化应激的线粒体蛋白质——热休克70 kDa蛋白9、过氧化物酶体增殖物激活受体6和抑制素——它们可能在中风损伤自我修复和PSD诱导的海马神经元损伤中起重要作用。这些发现为解读PSD对中风恢复产生不良影响的分子机制提供了新的见解。
