Mitochondrial Complex I Subunits are Altered in Rats with Neonatal Ventral Hippocampal Damage but not in Rats Exposed to Oxygen Restriction at Neonatal Age
Mitochondrial Complex I Subunits are Altered in Rats with Neonatal Ventral Hippocampal Damage but not in Rats Exposed to Oxygen Restriction at Neonatal Age
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DOI：
10.1007/s12031-008-9144-9
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发表时间：
2009-06-01
影响因子：
3.1
通讯作者：
Agam, Galila
中科院分区：
文献类型：
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作者：
Ben-Shachar, Dorit;Nadri, Carmit;Agam, Galila
一些独立的证据表明，精神分裂症患者的脑和外周存在线粒体功能障碍，包括线粒体发育不全、氧化磷酸化系统功能障碍和线粒体相关基因表达改变。为了揭示线粒体复合体I异常是精神分裂症的核心病理生理过程还是药物作用，我们研究了与精神分裂症神经发育假说相关的两种精神分裂症动物模型。在新生儿腹侧海马损伤大鼠模型和新生儿年龄暴露于缺氧的大鼠中，评估复合体I亚基24、51和75 kDa的蛋白水平。与假药治疗的大鼠相比，在精神分裂症的主要解剖基质——前额叶皮层中，新生儿海马腹侧病变诱发了青春期前复合物I的所有三个亚基的显著增加和青春期后复合物I的减少，而在扣带皮层中没有观察到变化。新生儿暴露于缺氧中不会影响前额皮质中三个亚基中的任何一个的蛋白质水平。复合体I亚基的表达呈年龄依赖性增加，新生儿海马腹侧病变扭曲了复合体I亚基在前额皮质的表达。在精神分裂症相关的神经发育大鼠模型中复合物I的改变似乎是脑区域和动物模型依赖的。这项研究的结果支持了先前的发现，即异常复合物I表达是精神分裂症的病理特征，而不是药物的影响。
Several independent lines of evidence suggest mitochondrial dysfunction in schizophrenia in brain and periphery, including mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system, and altered mitochondrial-related gene expression. In an attempt to decipher whether mitochondrial complex I abnormality in schizophrenia is a core pathophysiological process or is attributable to medication, we studied two animal models of schizophrenia related to the neurodevelopmental hypothesis of this disorder. Protein levels of complex I subunits, 24, 51, and 75 kDa, were assessed in neonatal ventral hippocampal lesion rat model and in rats exposed to hypoxia at a neonatal age. In the prefrontal cortex, a major anatomical substrate of schizophrenia, neonatal ventral hippocampal lesion induced a significant prepubertal increase and postpubertal decrease in all three subunits of complex I as compared to sham-treated rats, while no change was observed in the cingulate cortex. Neonatal exposure to hypoxia did not affect protein levels of any of the three subunits in the prefrontal cortex. An age-dependent increase in the expression of complex I subunits was observed, which was distorted in the prefrontal cortex by the neonatal ventral hippocampal lesion. Complex I alterations in schizophrenia-related neurodevelopmental rat models appear to be brain region and animal model dependent. The results of this study support previous findings suggesting abnormal complex I expression as a pathological characteristic of schizophrenia rather than an effect of medication.