Abstract:
OBJECTIVES:Extensive preclinical and clinical evidence suggests mitochondrial dysfunction in bipolar disorder. Studies of brain energy metabolism in bipolar disorder suggest an impairment of energy generation by mitochondrial oxidative phosphorylation. Lithium is an effective drug widely used in treating bipolar disorder, but its mechanism of action has remained uncertain. The aim of this study was to clarify the effect of lithium on mitochondrial oxidative phosphorylation. METHODS:We spectrophotometrically determined the activities of the respiratory chain complexes I + III [antimycin A-sensitive nicotinamide adenine dinucleotide (NADH) cytochrome c oxidorductase], complexes II + III (succinate cytochrome c oxidoreductase), succinate dehydrogenase, and complex IV [cytochrome c oxidase (COX)], and of the mitochondrial matrix enzyme citrate synthase in postmortem human brain cortex homogenates following exposure to lithium (up to 10 mM). RESULTS:Activities of complexes I + III and of complexes II + III were dose-dependently increased by lithium with maximum values at 1 mM (165%, p = 0.03, and 146%, p = 0.00002, of controls). Activity of succinate dehydrogenase remained unchanged up to 2 mM, but was raised at higher drug concentrations (maximum 220%, p = 0.01, of controls). In contrast, activity of COX was not significantly affected by the drug (decrease of 12% at 1 mM, p = 0.4). CONCLUSIONS:Our study suggests that lithium stimulates mitochondrial respiratory chain enzyme activities at clinically relevant concentrations. Lithium's effect on the mitochondrial respiratory chain presents further evidence of the pathophysiological significance of mitochondrial dysfunction in bipolar disorder. The effect may be relevant to the therapeutic efficacy of the drug by potentially reversing a disease-related alteration.
journal_name
Bipolar Disordjournal_title
Bipolar disordersauthors
Maurer IC,Schippel P,Volz HPdoi
10.1111/j.1399-5618.2009.00729.xsubject
Has Abstractpub_date
2009-08-01 00:00:00pages
515-22issue
5eissn
1398-5647issn
1399-5618pii
BDI729journal_volume
11pub_type
杂志文章abstract:OBJECTIVES:Bipolar disorder is frequently associated with cognitive impairment even during euthymia. Previous studies have reported significant impairments in functional and quality of life outcomes and a possible relationship between these variables and cognitive performance. Cognitive rehabilitation interventions hav...
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pub_type: 杂志文章,评审
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更新日期:2005-04-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2015-08-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
doi:10.1111/j.1399-5618.2008.00610.x
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2004.00117.x
更新日期:2004-12-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2009.00679.x
更新日期:2009-05-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1111/bdi.12595
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journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/j.1399-5618.2005.00203.x
更新日期:2005-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/bdi.12245
更新日期:2015-05-01 00:00:00
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journal_title:Bipolar disorders
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doi:
更新日期:2001-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1399-5618.2010.00807.x
更新日期:2010-05-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2012-02-01 00:00:00
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doi:10.1111/bdi.12493
更新日期:2017-06-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2007.00394.x
更新日期:2007-05-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2007.00413.x
更新日期:2007-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/bdi.12730
更新日期:2019-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2001-12-01 00:00:00
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doi:10.1111/bdi.12350
更新日期:2015-12-01 00:00:00
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更新日期:2010-06-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2008.00606.x
更新日期:2008-09-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2007.00423.x
更新日期:2007-06-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1034/j.1399-5618.2000.20303.x
更新日期:2000-09-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2006.00373.x
更新日期:2006-10-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/j.1399-5618.2007.00419.x
更新日期:2007-12-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章,评审
doi:10.1111/j.1399-5618.2012.01024.x
更新日期:2012-06-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1399-5618.2007.00530.x
更新日期:2007-09-01 00:00:00
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journal_title:Bipolar disorders
pub_type: 杂志文章
doi:10.1111/bdi.12110
更新日期:2013-11-01 00:00:00