药学学报, 2020, 55(2): 195-200
刘少博, 令狐婷, 高耀, 田俊生, 秦雪梅. 线粒体能量代谢障碍在抑郁症发病机制中的关键作用[J]. 药学学报, 2020, 55(2): 195-200.
LIU Shao-bo, LING-HU Ting, GAO Yao, TIAN Jun-sheng, QIN Xue-mei. The key role of mitochondrial energy metabolism disorder in the pathogenesis of depression[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 195-200.

刘少博1, 令狐婷1, 高耀1, 田俊生1,2, 秦雪梅1,2
1. 山西大学中医药现代研究中心, 山西 太原 030006;
2. 山西大学地产中药功效物质研究与利用山西省重点实验室, 山西 太原 030006
关键词:    抑郁症      线粒体      能量代谢障碍      发病机制     
The key role of mitochondrial energy metabolism disorder in the pathogenesis of depression
LIU Shao-bo1, LING-HU Ting1, GAO Yao1, TIAN Jun-sheng1,2, QIN Xue-mei1,2
1. Modern Research Center of Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China;
2. Key Laboratory of Research and Utilization of Functional Substances in Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China
Depression is a common mental illness with mood disorders as the main clinical feature. In recent years numerous studies have shown that mitochondrial function and structure are abnormal in patients with depression, and changes in mitochondrial ultrastructure can lead to energy metabolism disorders in the body. It is suggested that ‘mitochondrial energy metabolism disorder’ may be the pathogenesis of depression. This paper reviews the intrinsic association of mitochondrial energy metabolism with depression and notes potential mechanisms from the standpoint of mitochondrial structure and function on the molecular level. We provide a reference for understanding the pathogenesis of depression and identifying the possible targets of antidepressant drugs.
Key words:    depression    mitochondria    energy metabolism disorder    pathogenesis   
收稿日期: 2019-08-01
DOI: 10.16438/j.0513-4870.2019-0623
基金项目: 国家科技重大专项(2017ZX09301047);山西省科技重点研发计划(201903D321210);山西省重点实验室项目(201605D111004);山西省科技创新重点团队项目(201605D131045-18);山西省应用基础研究项目(201801D121291).
通讯作者: 田俊生,Tel:86-351-7019297,E-mail:jstian@sxu.edu.cn;秦雪梅,Tel:86-351-7018379,E-mail:qinxm@sxu.edu.cn
Email: jstian@sxu.edu.cn;qinxm@sxu.edu.cn
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[1] Yang Y, Cui Y, Sang K, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression[J]. Nature, 2018, 554:317-322.
[2] Cui Y, Yang Y, Ni Z, et al. Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression[J]. Nature, 2018, 554:323-327.
[3] Smith,Kerri. Mental health:a world of depression[J]. Nature, 2014, 515:180-191.
[4] Bai Y, Song L, Dai G, et al. Antidepressant effects of magnolia in a mouse model of depression induced by chronic corticosterone injection[J]. Steroids, 2018, 63:16-31.
[5] Labad J, Soria V, Salvat-Pujol N, et al. Hypothalamic-pituitary-adrenal axis activity in the comorbidity between obsessive-compulsive disorder and major depression[J]. Psychoneuroendocrinology, 2018, 93:20-28.
[6] Wang J Q, Mao L. The ERK Pathway:Molecular mechanisms and treatment of depression[J]. Mol Neurobiol, 2019, 56:6197-6205.
[7] Miyagishi H, Tsuji M, Saito A, et al. Inhibitory effect of yokukansan on the decrease in the hippocampal excitatory amino acid transporter EAAT2 in stress-maladaptive mice[J]. J Tradit Complement Med, 2017, 7:371-374.
[8] Gardner A, Boles RG. Mitochondrial energy depletion in depression with somatization[J]. Psychother Psychosomat, 2008, 77:127-129.
[9] Allaman I, Magistretti PJ, Martin JL. Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes[J]. Curr Drug Targets, 2013, 14:157-169.
[10] Amini-Khoei H, Mohammadi-Asl A, Amiri S, et al. Oxytocin mitigated the depressive-like behaviors of maternal separation stress through modulating mitochondrial function and neuroinflammation[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2017, 76:169-178.
[11] Yuan QJ, Guo JY, Wang JW, et al. Study on syndrome of stagnation of liver qi and spleen deficiency in depression based on corticosterone-inflammation-mitochondrial network and effects of Xingpi Jieyu Decoction[J]. China J Tradit Chin Med Pharm (中华中医药杂志), 2017, 32:2241-2245.
[12] Villa RF, Ferrari F, Gorini A, et al. Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria[J]. Neuroscience, 2016, 330:326-334.
[13] Karabatsiakis A, Böck C, Salinasmanrique J, et al. Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression[J]. Transl Psychiatry, 2014, 4:397-410.
[14] GlOmbik K, Stachowicz A, Olszanecki R, et al. The effect of chronic tianeptine administration on the brain mitochondria:direct links with an animal model of depression[J]. Mol Neurobiol, 2016, 10:7351-7362.
[15] Madrigal JL, Olivenza R, Moro MA, et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain.[J]. Neuropsychopharmacology, 2001, 24:420-429.
[16] Aguiar AS Jr, Stragier E, da Luz Scheffer D, et al. Effects of exercise on mitochondrial function, neuroplasticity and anxio-depressive behavior of mice[J]. Neuroscience, 2014, 271:56-63.
[17] de Sousa RT, Streck EL, Zanetti MV, et al. Lithium increases leukocyte mitochondrial complex I activity in bipolar disorder during depressive episodes[J]. Psychopharmacology, 2015, 232:245-250.
[18] Ben-Shachar D, Karry R. Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression[J]. PLoS One, 2008, 3:76-92.
[19] Yang X, Zhang Y, Xu H, et al. Neuroprotection of coenzyme Q10 in neurodegenerative diseases[J]. Curr Topics Med Chem, 2016, 16:432-444.
[20] Li L, Du J, Lian Y, et al. Protective effects of coenzyme Q10 against hydrogen peroxide-induced oxidative stress in PC12 cell:the role of Nrf2 and antioxidant enzymes[J]. Cell Mol Neurobiol, 2016, 36:103-111.
[21] Sakhaie MH, Soleimani M, Pirhajati V, et al. Coenzyme Q10 ameliorates trimethyltin chloride neurotoxicity in experimental model of injury in dentate gyrus of hippocampus:a histopathological and behavioral study[J]. Iran Red Crescent Med J, 2016, 18:297-310.
[22] Vaclav V, Jana V. Combination therapy with glucan and coenzyme Q10 in murine experimental autoimmune disease and cancer[J]. Anticancer Res, 2018, 38:3291-3297.
[23] Aboul-fotouh S. Coenzyme Q10 displays antidepressant-like activity with reduction of hippocampal oxidative/nitrosative DNA damage in chronically stressed rats[J]. Pharmacol Biochem Behav, 2013, 104:105-112.
[24] Ghorbanmehr N, Salehnia M, Amooshahi M. The effects of sodium selenite on mitochondrial DNA copy number and reactive oxygen species levels of in vitro matured mouse oocytes[J]. Cell J, 2018, 20:396-402.
[25] Tymofiyeva O, Henje EB, Ho TC, et al. High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression[J]. J Affect Disord, 2018, 232:283-290.
[26] Kasahara T, Kubota M, Miyauchi T, et al. Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes[J]. Mol Psychiatry, 2006, 11:577-593.
[27] Cai N, Chang S, Li Y, et al. Molecular signatures of major depression[J]. Curr Biol, 2015, 25:1146-1156.
[28] Kato T, Kunugi H, Nanko S, et al. Mitochondrial DNA polymorphisms in bipolar disorder[J]. J Affect Disord, 2001, 62:151-164.
[29] Sun J, Li J, Guo Z, et al. Overexpression of pyruvate dehydrogenase E1α subunit inhibits warburg effect and induces cell apoptosis through mitochondria-mediated pathway in hepatocellular carcinoma[J]. Oncol Res, 2019, 27:407-414.
[30] Gardani CFF, Cappellari AR, De Souza JB, et al. Hydrolysis of ATP, ADP, and AMP is increased in blood plasma of prostate cancer patients[J]. Purinergic Signal, 2019, 15:95-105.
[31] Andersen JV, Jakobsen E, Waagepetersen HS, et al. Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non-synaptic mouse brain mitochondria[J]. J Neurosci Res, 2019, 97:961-974.
[32] Kato T, Takahashi S, Shioiri T, et al. Alterations in brain phosphorous metabolism in bipolar disorder detected by in vivo 31P and 7Li magnetic resonance spectroscopy[J]. J Affect Disord, 1993, 27:53-59.
[33] Kato T, Inubushi T, Kato N. Magnetic resonance spectroscopy in affective disorders[J]. J Neuropsychiatry Clin Neurosci, 1998, 10:133-147.
[34] Deicken RF, Weiner MW, Fein G. Decreased temporal lobe phosphomonoesters in bipolar disorder[J]. J Affect Disord, 1995, 33:195-199.
[35] Esmaeili MH, Bahari B, Salari AA. ATP-sensitive potassium-channel inhibitor glibenclamide attenuates HPA axis hyperactivity, depression- and anxiety-related symptoms in a rat model of Alzheimer's disease[J]. Brain Res Bull, 2018, 137:265-276.
[36] Cao X, Li LP, Wang Q, et al. Astrocyte-derived ATP modulates depressive-like behaviors[J]. Nat Med, 2013, 19:773-777.
[37] Gardner A, Johansson A, Wibom R, et al. Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients[J]. J Affect Disord, 2003, 76:55-68.
[38] Tobe EH. Mitochondrial dysfunction, oxidative stress, and major depressive disorder[J]. Neuropsychiatr Dis Treat, 2013, 9:567-573.
[39] Moreno J, Gaspar E, Lópezbello G, et al. Increase in nitric oxide levels and mitochondrial membrane potential in platelets of untreated patients with major depression[J]. Psychiatry Res, 2013, 209:447-452.
[40] Phillips C, Fahimi A. Immune and neuroprotective effects of physical activity on the brain in depression[J]. Front Neurosci, 2018, 12:498-512.
[41] Zhang L, Wang QD, Shi HM, et al. Influence of ferulic acid on the pain-depression dyad induced by reserpine[J]. Acta Pharm Sin (药学学报), 2013, 48:32-37.
[42] Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism:key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease[J]. J Neurosci Res, 2017, 95:943-972.
[43] Chen JL. The protective effect and mechanism of Compound Chaigui Fang on Corticosterone-Induced Poorly Differentiated PC12 Cells Injury (复方柴归方抗抑郁机制研究)[D]. Taiyuan:Shanxi University, 2016.
[44] Ding X, Jing LL, Sun XG, et al. Energy metabolism disorder and spleen deficiency being the key pathogenesis of depression[J]. J Tradit Chin Med (中医杂志), 2016, 57:924-926.
[45] Li Y, Yu Y, et al. Effect of Xingpi Jieyu decoction on serum IL-8 and liver MDA, mtDNA and ATP levels in CUMS depression model rats[J]. Global Tradit Chin Med (环球中医药), 2019, 12:497-501.
[46] Higashi RM, Fan WM, Lorkiewicz PK, et al. Stable isotope-labeled tracers for metabolic pathway elucidation by GC-MS and FT-MS[J]. Methods Mol Biol, 2014, 1198:147-167.
[47] O'Brien KO, Abrams SA. Using stable isotope tracers to study bone metabolism in children[J]. J Physiol, 2019, 597:1311-1319.
[48] David H, Pedro GM, Mario FF, et al. Melatonin decreases glucose metabolism in prostate cancer cells:a 13C stable isotope-resolved metabolomic study[J]. Int J Mol Sci, 2017, 18:1620-1639.