Lithium increases leukocyte mitochondrial complex I activity in bipolar disorder during depressive episodes
Lithium increases leukocyte mitochondrial complex I activity in bipolar disorder during depressive episodes
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DOI：
10.1007/s00213-014-3655-6
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发表时间：
2015-01-01
影响因子：
3.4
通讯作者：
Machado-Vieira, Rodrigo
中科院分区：
文献类型：
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作者：
de Sousa, Rafael T.;Streck, Emilio L.;Machado-Vieira, Rodrigo
不同的证据表明，线粒体功能障碍可能涉及双相情感障碍（BD）的病理生理学。线粒体电子传递链（ETC）是评估线粒体功能的关键靶点，但其活性从未在未用药的BD或情绪发作期间进行过评估。此外，锂已显示在临床前模型和BD受试者的死后脑中增加ETC基因表达/活性，但迄今为止，目前还没有研究评价锂对体内ETC活性的直接影响，本研究旨在评价BD患者急性抑郁发作时白细胞ETC复合物I-IV的活性在抑郁发作期间具有短期BD的受试者（n = 25）用锂治疗6周。在基线和终点收集白细胞，评估线粒体ETC复合物I-IV活性，并与年龄匹配的健康对照组（n = 24）进行比较。锂显著增加线粒体复合物I活性，从基线到终点（p = 0.02），6周后其他复合物无变化。此外，治疗后血浆锂水平与线粒体复合物I活性显著相关（p = 0.003）。线粒体复合物I-IV的活动并没有不同的抑郁发作在BD相比，健康controls.Our的研究结果表明，第一次在体内增加线粒体ETC复合物I的活动后，锂治疗在BD，这是正相关的血浆锂水平。进一步的研究是必要的，以澄清这个目标在神经保护相关药物开发的潜在作用。
Different lines of evidence suggest that mitochondrial dysfunction may be implicated in bipolar disorder (BD) pathophysiology. Mitochondrial electron transport chain (ETC) is a key target to evaluate mitochondrial function, but its activity has never been assessed in unmedicated BD or during mood episodes. Also, lithium has been shown to increase ETC gene expression/activity in preclinical models and in postmortem brains of BD subjects, but to date, no study has evaluated lithium's direct effects on ETC activity in vivo.This study aims to evaluate leukocyte ETC complexes I-IV activities in acute depressive episode in BD (compared to controls) and the effect of lithium treatment on ETC activity.Subjects with short-term BD during a depressive episode (n = 25) were treated for 6 weeks with lithium. Leukocytes were collected at baseline and endpoint and mitochondrial ETC complexes I-IV activities were evaluated and compared to age-matched healthy controls (n = 24).Lithium significantly increased mitochondrial complex I activity from baseline to endpoint (p = 0.02), with no changes in other complexes after 6 weeks. Also, plasma lithium levels were significantly correlated to mitochondrial complex I activity after treatment (p = 0.003). Mitochondrial complexes I-IV activities did not differ during depressive episodes in BD compared to healthy controls.Our findings demonstrate for the first time an increase in mitochondrial ETC complex I activity in vivo after lithium treatment in BD, which was positively associated with plasma lithium levels. Further studies are warranted to clarify the potential role of this target in neuroprotection-related drug development.