Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder.
Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder.
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线粒体DNA拷贝数、线粒体DNA总体细胞缺失、复合体I活性、突触数和突触线粒体数在精神分裂症和双相情感障碍中改变。
DOI：
10.1038/s41398-022-02127-1
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发表时间：
2022-08-30
影响因子：
6.8
通讯作者：
Vawter, Marquis P.
中科院分区：
文献类型：
--
作者：
Das, Sujan C.;Hjelm, Brooke E.;Rollins, Brandi L.;Sequeira, Adolfo;Morgan, Ling;Omidsalar, Audrey A.;Schatzberg, Alan F.;Barchas, Jack D.;Lee, Francis S.;Myers, Richard M.;Watson, Stanley J.;Akil, Huda;Bunney, William E.;Vawter, Marquis P.
线粒体功能障碍是精神分裂症和双相情感障碍的病理生理学中涉及的神经生物学现象，其可以协同影响突触神经传递。我们假设精神分裂症和双相情感障碍在线粒体和突触水平上共享分子改变。研究了正常人（CON）和精神分裂症患者（SZ）死后背外侧前额叶皮层（DLPFC）、上级颞回（STG）、初级视皮层（V1）和视核（NAc）的线粒体DNA拷贝数（CN）、线粒体DNA共同缺失（CD）、线粒体DNA总缺失、复合物I活性、突触数和突触线粒体数。双相情感障碍（BD）结果表明：（1）SZ和BD的DLPFC的mtDNA CN显著升高，STG降低，而V1和NAc无变化，（2）SZ和BD的DLPFC的mtDNA CD显著升高，STG、V1和NAc无变化;（iii）SZ和BD的DLPFC的总缺失负荷显著更高，而SZ和BD的STG、V1和NAc的总缺失负荷不变;（iv）SZ和BD的DLPFC中复合物I活性显著较低，这是由药物的存在驱动的，而STG、V1和NAc没有改变。此外，通过ELISA，复合物I蛋白浓度在SZ和BD受试者的三个皮质区域中降低;（V）SZ和BD两者的DLPFC中的突触数量减少，而与雌性对照相比，雌性SZ和雌性BD中的突触线粒体数量显著降低。总的来说，这些发现将为更好地理解精神分裂症和双相情感障碍的病理生理学以进行治疗干预铺平道路。
Mitochondrial dysfunction is a neurobiological phenomenon implicated in the pathophysiology of schizophrenia and bipolar disorder that can synergistically affect synaptic neurotransmission. We hypothesized that schizophrenia and bipolar disorder share molecular alterations at the mitochondrial and synaptic levels. Mitochondria DNA (mtDNA) copy number (CN), mtDNA common deletion (CD), mtDNA total deletion, complex I activity, synapse number, and synaptic mitochondria number were studied in the postmortem human dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), primary visual cortex (V1), and nucleus accumbens (NAc) of controls (CON), and subjects with schizophrenia (SZ), and bipolar disorder (BD). The results showed (i) the mtDNA CN is significantly higher in DLPFC of both SZ and BD, decreased in the STG of BD, and unaltered in V1 and NAc of both SZ and BD; (ii) the mtDNA CD is significantly higher in DLPFC of BD while unaltered in STG, V1, and NAc of both SZ and BD; (iii) The total deletion burden is significantly higher in DLPFC in both SZ and BD while unaltered in STG, V1, and NAc of SZ and BD; (iv) Complex I activity is significantly lower in DLPFC of both SZ and BD, which is driven by the presence of medications, with no alteration in STG, V1, and NAc. In addition, complex I protein concentration, by ELISA, was decreased across three cortical regions of SZ and BD subjects; (v) The number of synapses is decreased in DLPFC of both SZ and BD, while the synaptic mitochondria number was significantly lower in female SZ and female BD compared to female controls. Overall, these findings will pave the way to understand better the pathophysiology of schizophrenia and bipolar disorder for therapeutic interventions.
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影响因子：
4.5
作者：
Mamdani, Firoza;Rollins, Brandi;Morgan, Ling;Sequeira, P. Adolfo;Vawter, Marquis P.
通讯作者：
Vawter, Marquis P.
DOI：
10.1159/000441252
发表时间：
2015-12
期刊：
Molecular neuropsychiatry
影响因子：
--
作者：
Hjelm BE;Rollins B;Mamdani F;Lauterborn JC;Kirov G;Lynch G;Gall CM;Sequeira A;Vawter MP
通讯作者：
Vawter MP
DOI：
10.1176/appi.ajp.2020.19111210
发表时间：
2020-12-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Glausier JR;Enwright JF 3rd;Lewis DA
通讯作者：
Lewis DA
影响因子：
15.1
作者：
Angrand, Loic;Boukouaci, Wahid;Tamouza, Ryad
通讯作者：
Tamouza, Ryad
影响因子：
5.3
作者：
Frahm, T;Mohamed, SA;Meissner, C
通讯作者：
Meissner, C