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Cited by 110Tryptophan and brain disordersNeuroinflammation and Neurodegeneration MechanismsTreatment of Major Depression

Mitochondria, Microglia, and the Immune System—How Are They Linked in Affective Disorders?

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Culmsee, Carsten, Michels, Susanne, Scheu, Stefanie, Arolt, Volker, Dannlowski, Udo, Alferink, Judith·2019·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2018.00739PMC PMC6333629
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Abstract

Major depressive disorder (MDD) is a severe mood disorder and frequently associated with alterations of the immune system characterized by enhanced levels of circulating pro-inflammatory cytokines and microglia activation in the brain. Increasing evidence suggests that dysfunction of mitochondria may play a key role in the pathogenesis of MDD. Mitochondria are regulators of numerous cellular functions including energy metabolism, maintenance of redox and calcium homeostasis, and cell death and therefore modulate many facets of the innate immune response. In depression-like behavior of rodents, mitochondrial perturbation and release of mitochondrial components have been shown to boost cytokine production and neuroinflammation. On the other hand, pro-inflammatory cytokines may influence mitochondrial functions such as oxidative phosphorylation, production of adenosine triphosphate, and reactive oxygen species, thereby aggravating inflammation. There is strong interest in a better understanding of immunometabolic pathways in MDD that may serve as diagnostic markers and therapeutic targets. Here, we review the interaction between mitochondrial metabolism and innate immunity in the pathophysiology of MDD. We specifically focus on immunometabolic processes that govern microglial and peripheral myeloid cell functions, both cellular components involved in neuroinflammation in depression-like behavior. We finally discuss microglial polarization and associated metabolic states in depression-associated behavior and in MDD.

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  1. [1]Greden JF. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry (2001) 62(Suppl. 22): 5– 9. 11599650
  2. [2]Greenberg PE Kessler RC Birnbaum HG Leong SA Lowe SW Berglund PA. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry (2003) 64: 1465– 75. 10.4088/JCP.v64n1211 14728109 · DOI · Paper page
  3. [3]Nemeroff CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry (2007) 68(Suppl. 8): 17– 25. 17640154
  4. [4]Kupfer DJ Frank E Phillips ML. Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet (2012) 379: 1045– 55. 10.1016/S0140-6736(11)60602-8 22189047 PMC3397431 · DOI · Paper page
  5. [5]Direk N Williams S Smith JA Ripke S Air T Amare AT. An analysis of two genome-wide association meta-analyses identifies a new locus for broad depression phenotype. Biol Psychiatry (2017) 82: 322– 9. 10.1016/j.biopsych.2016.11.013 28049566 PMC5462867 · DOI
  6. [6]Yu C Baune BT Wong ML Licinio J. Investigation of short tandem repeats in major depression using whole-genome sequencing data. J Affect Disord. (2018) 232: 305– 9. 10.1016/j.jad.2018.02.046 29501989 · DOI
  7. [7]Mills NT Scott JG Wray NR Cohen-Woods S Baune BT. Research review: the role of cytokines in depression in adolescents: a systematic review. J Child Psychol Psychiatry Allied Discip. (2013) 54: 816– 35. 10.1111/jcpp.12080 24027786 · DOI
  8. [8]Prager G Hadamitzky M Engler A Doenlen R Wirth T Pacheco-Lopez G Amygdaloid signature of peripheral immune activation by bacterial lipopolysaccharide or staphylococcal enterotoxin B. J Neuroimmune Pharmacol. (2013) 8: 42– 50. 10.1007/s11481-012-9373-0 22639228 · DOI
  9. [11]Dantzer R. Cytokine, sickness behavior, and depression. Neurol Clin. (2006) 24: 441– 60. 10.1016/j.ncl.2006.03.003 16877117 PMC2909644 · DOI · Paper page
  10. [12]Maes M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuro Psychopharmacol Biol Psychiatry (1995) 19: 11– 38. 10.1016/0278-5846(94)00101-M 7708925 · DOI · Paper page
  11. [13]Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. (2008) 29: 287– 91. 18580840
  12. [15]Bauer ME Teixeira AL. Inflammation in psychiatric disorders: what comes first? Ann NY Acad Sci. (2018). [Epub ahead of print]. 10.1111/nyas.13712 29752710 · DOI · Paper page
  13. [16]Eyre HA Stuart MJ Baune BT. A phase-specific neuroimmune model of clinical depression. Prog Neuro Psychopharmacol Biol Psychiatry (2014) 54: 265– 74. 10.1016/j.pnpbp.2014.06.011 24999185 · DOI
  14. [17]Miller AH Raison CL. Are anti-inflammatory therapies viable treatments for psychiatric disorders?: Where the rubber meets the road. JAMA Psychiatry (2015) 72: 527– 8. 10.1001/jamapsychiatry.2015.22 25853989 PMC5542670 · DOI · Paper page
  15. [18]Bufalino C Hepgul N Aguglia E Pariante CM. The role of immune genes in the association between depression and inflammation: a review of recent clinical studies. Brain Behav Immun. (2013) 31: 31– 47. 10.1016/j.bbi.2012.04.009 22580182 · DOI · Paper page
  16. [19]Medzhitov R Shevach EM Trinchieri G Mellor AL Munn DH Gordon S. Highlights of 10 years of immunology in Nature Reviews Immunology. Nat Rev Immunol. (2011) 11: 693– 702. 10.1038/nri3063 21941295 PMC3703536 · DOI
  17. [20]Geissmann F Manz MG Jung S Sieweke MH Merad M Ley K. Development of monocytes, macrophages, and dendritic cells. Science (2010) 327: 656– 61. 10.1126/science.1178331 20133564 PMC2887389 · DOI · Paper page
  18. [21]Takeuchi O Akira S. Pattern recognition receptors and inflammation. Cell (2010) 140: 805– 20. 10.1016/j.cell.2010.01.022 20303872 · DOI · Paper page
  19. [23]Rock KL Latz E Ontiveros F Kono H. The sterile inflammatory response. Ann Rev Immunol. (2010) 28: 321– 42. 10.1146/annurev-immunol-030409-101311 20307211 PMC4315152 · DOI · Paper page
  20. [26]Boyapati RK Tamborska A Dorward DA Ho GT. Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases. F1000Res. (2017) 6: 169. 10.12688/f1000research.10397.1 28299196 PMC5321122 · DOI
  21. [27]Shimada K Crother TR Karlin J Dagvadorj J Chiba N Chen S. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity (2012) 36: 401– 14. 10.1016/j.immuni.2012.01.009 22342844 PMC3312986 · DOI · Paper page
  22. [29]Heneka MT McManus RM Latz E. Inflammasome signalling in brain function and neurodegenerative disease. Nat Rev Neurosci. (2018) 19: 610– 21. 10.1038/s41583-018-0055-7 30206330 · DOI · Paper page
  23. [30]Nakahira K Haspel JA Rathinam VA Lee SJ Dolinay T Lam HC. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. (2011) 12: 222– 30. 10.1038/ni.1980 21151103 PMC3079381 · DOI · Paper page
  24. [31]Zhou R Yazdi AS Menu P Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature (2011) 469: 221– 5. 10.1038/nature09663 21124315 · DOI · Paper page
  25. [32]Fleshner M Frank M Maier SF. Danger signals and inflammasomes: stress-evoked sterile inflammation in mood disorders. Neuropsychopharmacology (2017) 42: 36– 45. 10.1038/npp.2016.125 27412959 PMC5143484 · DOI · Paper page
  26. [33]Sadatomi D Nakashioya K Mamiya S Honda S Kameyama Y Yamamura Y. Mitochondrial function is required for extracellular ATP-induced NLRP3 inflammasome activation. J Biochem. (2017) 161: 503– 12. 10.1093/jb/mvw098 28096454 · DOI
  27. [36]Tschopp J Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. (2010) 10: 210– 5. 10.1038/nri2725 20168318 · DOI
  28. [37]Schroder K Tschopp J. The inflammasomes. Cell (2010) 140: 821– 32. 10.1016/j.cell.2010.01.040 20303873 · DOI · Paper page
  29. [38]Zhong Z Liang S Sanchez-Lopez E He F Shalapour S Lin XJ. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature (2018) 560: 198– 203. 10.1038/s41586-018-0372-z 30046112 PMC6329306 · DOI · Paper page
  30. [39]Gibney SM Drexhage HA. Evidence for a dysregulated immune system in the etiology of psychiatric disorders. J Neuroimmune Pharmacol. (2013) 8: 900– 20. 10.1007/s11481-013-9462-8 23645137 · DOI
  31. [40]Maes M Yirmyia R Noraberg J Brene S Hibbeln J Perini G The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metabol Brain Dis. (2009) 24: 27– 53. 10.1007/s11011-008-9118-1 19085093 · DOI · Paper page
  32. [41]Dantzer R O'Connor JC Lawson MA Kelley KW. Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology (2011) 36: 426– 36. 10.1016/j.psyneuen.2010.09.012 21041030 PMC3053088 · DOI · Paper page
  33. [42]Raison CL Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. (2011) 13: 467– 75. 10.1007/s11920-011-0232-0 21927805 PMC3285451 · DOI · Paper page
  34. [44]Dowlati Y Herrmann N Swardfager W Liu H Sham L Reim EK. A meta-analysis of cytokines in major depression. Biol. Psychiatry (2010) 67: 446– 57. 10.1016/j.biopsych.2009.09.033 20015486 · DOI · Paper page
  35. [45]Kohler CA Freitas TH Stubbs B Maes M Solmi M Veronese N. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. (2018) 55: 4195– 206. 10.1007/s12035-017-0632-1 28612257 · DOI · Paper page
  36. [46]Baune BT Konrad C Grotegerd D Suslow T Birosova E Ohrmann P. Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain. J Neuroinflamm. (2012) 9: 125. 10.1186/1742-2094-9-125 22695063 PMC3464888 · DOI
  37. [47]Baune BT Konrad C Grotegerd D Suslow T Ohrmann P Bauer J. Tumor necrosis factor gene variation predicts hippocampus volume in healthy individuals. Biol. Psychiatry (2012) 72: 655– 62. 10.1016/j.biopsych.2012.04.002 22554453 · DOI
  38. [50]Redlich R Stacey D Opel N Grotegerd D Dohm K Kugel H. Evidence of an IFN-gamma by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli. Psychoneuroendocrinology (2015) 62: 66– 73. 10.1016/j.psyneuen.2015.08.008 26313134 · DOI
  39. [51]Opel N Redlich R Zwanzger P Grotegerd D Arolt V Heindel W. Hippocampal atrophy in major depression: a function of childhood maltreatment rather than diagnosis? Neuropsychopharmacology (2014) 39: 2723– 31. 10.1038/npp.2014.145 24924799 PMC4200502 · DOI · Paper page
  40. [52]Hazel NA Hammen C Brennan PA Najman J. Early childhood adversity and adolescent depression: the mediating role of continued stress. Psychol Med. (2008) 38: 581– 9. 10.1017/S0033291708002857 18261247 · DOI
  41. [53]Krishnan V Nestler EJ. The molecular neurobiology of depression. Nature (2008) 455: 894– 902. 10.1038/nature07455 18923511 PMC2721780 · DOI · Paper page
  42. [56]Cattaneo A Macchi F Plazzotta G Veronica B Bocchio-Chiavetto L Riva MA. Inflammation and neuronal plasticity: a link between childhood trauma and depression pathogenesis. Front Cell Neurosci. (2015) 9: 40. 10.3389/fncel.2015.00040 25873859 PMC4379909 · DOI · Paper page
  43. [59]Hussein S Dalton B Willmund GD Ibrahim MAA Himmerich H. A systematic review of tumor necrosis factor-alpha in post-traumatic stress disorder: evidence from human and animal studies. Psychiatr Danub. (2017) 29: 407– 20. 10.24869/psyd.2017.407 29197197 · DOI · Paper page
  44. [60]Rao NP Venkatasubramanian G Ravi V Kalmady S Cherian A Yc JR. Plasma cytokine abnormalities in drug-naive, comorbidity-free obsessive-compulsive disorder. Psychiatry Res. (2015) 229: 949– 52. 10.1016/j.psychres.2015.07.009 26187339 · DOI
  45. [62]Kircher T Wohr M Nenadic I Schwarting R Schratt G Alferink J. Neurobiology of the major psychoses: a translational perspective on brain structure and function-the FOR2107 consortium. Eur Arch Psychiatry Clin Neurosci. (2018). [Epub ahead of print]. 10.1007/s00406-018-0943-x 30267149 · DOI
  46. [63]Krishnan V Berton O Nestler E. The use of animal models in psychiatric research and treatment. Am J Psychiatry (2008) 165: 1109. 10.1176/appi.ajp.2008.08071076 18765492 · DOI
  47. [64]Toyoda A. Social defeat models in animal science: what we have learned from rodent models. Anim Sci J. (2017) 88: 944– 52. 10.1111/asj.12809 28436163 PMC5518448 · DOI
  48. [65]Ramirez K Fornaguera-Trias J Sheridan JF. Stress-induced microglia activation and monocyte trafficking to the brain underlie the development of anxiety and depression. Curr Top Behav Neurosci. (2017) 31: 155– 72. 10.1007/7854_2016_25 27352390 · DOI
  49. [66]Engler H Bailey MT Engler A Sheridan JF. Effects of repeated social stress on leukocyte distribution in bone marrow, peripheral blood and spleen. J Neuroimmunol. (2004) 148: 106– 15. 10.1016/j.jneuroim.2003.11.011 14975591 · DOI · Paper page
  50. [67]Wohleb ES Powell ND Godbout JP Sheridan JF. Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J Neurosci. (2013) 33: 13820– 33. 10.1523/JNEUROSCI.1671-13.2013 23966702 PMC3755721 · DOI · Paper page
  51. [68]Zheng X Ma S Kang A Wu M Wang L Wang Q. Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice. Sci Rep. (2016) 6: 19406. 10.1038/srep19406 26783261 PMC4725984 · DOI
  52. [69]Ambree O Ruland C Scheu S Arolt V Alferink J. Alterations of the innate immune system in susceptibility and resilience after social defeat stress. Front Behav Neurosci. (2018) 12: 141. 10.3389/fnbeh.2018.00141 30057531 PMC6053497 · DOI
  53. [70]Li MX Zheng HL Luo Y He JG Wang W Han J. Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs. Mol Psychiatry (2018) 23: 556– 68. 10.1038/mp.2017.76 28416811 PMC5822452 · DOI
  54. [71]Zhang Y Liu L Peng YL Liu YZ Wu TY Shen XL. Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors. CNS Neurosci Ther. (2014) 20: 119– 24. 10.1111/cns.12170 24279434 PMC6493120 · DOI · Paper page
  55. [72]Burfeind KG Zhu X Levasseur PR Michaelis KA Norgard MA Marks DL. TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia. Brain Behav Immun. (2018) 73: 364– 74. 10.1016/j.bbi.2018.05.021 29852290 PMC6129432 · DOI
  56. [73]Le Thuc O Cansell C Bourourou M Denis RG Stobbe K Devaux N. Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation. EMBO Rep. (2016) 17: 1738– 52. 10.15252/embr.201541499 27733491 PMC5283585 · DOI
  57. [75]Tay TL Bechade C D'Andrea I St-Pierre MK Henry MS Roumier A. Microglia gone rogue: impacts on psychiatric disorders across the lifespan. Front Mol Neurosci. (2017) 10: 421. 10.3389/fnmol.2017.00421 29354029 PMC5758507 · DOI
  58. [76]Kalkman HO Feuerbach D. Antidepressant therapies inhibit inflammation and microglial M1-polarization. Pharmacol Ther. (2016) 163: 82– 93. 10.1016/j.pharmthera.2016.04.001 27101921 · DOI · Paper page
  59. [78]Ransohoff RM Brown MA. Innate immunity in the central nervous system. J Clin Invest. (2012) 122: 1164– 71. 10.1172/JCI58644 22466658 PMC3314450 · DOI · Paper page
  60. [79]Singhal G Baune BT. Microglia: an interface between the loss of neuroplasticity and depression. Front Cell Neurosci. (2017) 11: 270. 10.3389/fncel.2017.00270 28943841 PMC5596091 · DOI
  61. [80]Tay TL Savage JC Hui CW Bisht K Tremblay ME. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. J Physiol. (2017) 595: 1929– 45. 10.1113/JP272134 27104646 PMC5350449 · DOI · Paper page
  62. [81]Napoli I Neumann H. Microglial clearance function in health and disease. Neuroscience (2009) 158: 1030– 8. 10.1016/j.neuroscience.2008.06.046 18644426 · DOI
  63. [82]Amici SA Dong J Guerau-de-Arellano M. Molecular mechanisms modulating the phenotype of macrophages and microglia. Front Immunol. (2017) 8: 1520. 10.3389/fimmu.2017.01520 29176977 PMC5686097 · DOI
  64. [83]Yrondi A Aouizerate B El-Hage W Moliere F Thalamas C Delcourt N. Assessment of translocator protein density, as marker of neuroinflammation, in major depressive disorder: a pilot, multicenter, comparative, controlled, Brain PET Study (INFLADEP Study). Front. Psychiatry (2018) 9: 326. 10.3389/fpsyt.2018.00326 30087626 PMC6066663 · DOI · Paper page
  65. [84]Setiawan E Attwells S Wilson AA Mizrahi R Rusjan PM Miler L. Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study. Lancet Psychiatry (2018) 5: 339– 47. 10.1016/S2215-0366(18)30048-8 29496589 · DOI
  66. [85]Norden DM Godbout JP. Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol. (2013) 39: 19– 34. 10.1111/j.1365-2990.2012.01306.x 23039106 PMC3553257 · DOI · Paper page
  67. [86]Steiner J Bielau H Brisch R Danos P Ullrich O Mawrin C. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res. (2008) 42: 151– 7. 10.1016/j.jpsychires.2006.10.013 17174336 · DOI · Paper page
  68. [87]Schnieder TP Trencevska I Rosoklija G Stankov A Mann JJ Smiley J. Microglia of prefrontal white matter in suicide. J Neuropathol Exp Neurol. (2014) 73: 880– 90. 10.1097/NEN.0000000000000107 25101704 PMC4141011 · DOI · Paper page
  69. [88]Yirmiya R Rimmerman N Reshef R. Depression as a microglial disease. Trends Neurosci. (2015) 38: 637– 58. 10.1016/j.tins.2015.08.001 26442697 · DOI · Paper page
  70. [89]Liu Y Holdbrooks AT De Sarno P Rowse AL Yanagisawa LL McFarland BC. Therapeutic efficacy of suppressing the Jak/STAT pathway in multiple models of experimental autoimmune encephalomyelitis. J Immunol. (2014) 192: 59– 72. 10.4049/jimmunol.1301513 24323580 PMC3934829 · DOI
  71. [90]Colle R de Larminat D Rotenberg S Hozer F Hardy P Verstuyft C. PPAR-gamma agonists for the treatment of major depression: a review. Pharmacopsychiatry (2017) 50: 49– 55. 10.1055/s-0042-120120 27978584 · DOI
  72. [91]English C Aloi JJ. New FDA-approved disease-modifying therapies for multiple sclerosis. Clin Ther. (2015) 37: 691– 715. 10.1016/j.clinthera.2015.03.001 25846320 · DOI
  73. [92]Su F Yi H Xu L Zhang Z. Fluoxetine and S-citalopram inhibit M1 activation and promote M2 activation of microglia in vitro. Neuroscience (2015) 294: 60– 8. 10.1016/j.neuroscience.2015.02.028 25711936 · DOI
  74. [93]Alcocer-Gomez E Ulecia-Moron C Marin-Aguilar F Rybkina T Casas-Barquero N Ruiz-Cabello J. Stress-induced depressive behaviors require a functional NLRP3 inflammasome. Mol Neurobiol. (2016) 53: 4874– 82. 10.1007/s12035-015-9408-7 26362308 · DOI · Paper page
  75. [94]Zhao Q Wu X Yan S Xie X Fan Y Zhang J. The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARgamma-mediated alteration of microglial activation phenotypes. J Neuroinflam. (2016) 13: 259. 10.1186/s12974-016-0728-y 27716270 PMC5051050 · DOI
  76. [95]Kenis G Maes M. Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol. (2002) 5: 401– 12. 10.1017/S1461145702003164 12466038 · DOI · Paper page
  77. [96]Herculano-Houzel S. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution. PLoS ONE (2011) 6: e17514. 10.1371/journal.pone.0017514 21390261 PMC3046985 · DOI · Paper page
  78. [98]Kato T. Role of mitochondrial DNA in calcium signaling abnormality in bipolar disorder. Cell Calcium (2008) 44: 92– 102. 10.1016/j.ceca.2007.11.005 18177933 · DOI
  79. [99]Manji H Kato T Di Prospero NA Ness S Beal MF Krams M. Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci. (2012) 13: 293– 307. 10.1038/nrn3229 22510887 · DOI
  80. [101]Morava E Kozicz T. Mitochondria and the economy of stress (mal)adaptation. Neurosci Biobehav Rev. (2013) 37: 668– 80. 10.1016/j.neubiorev.2013.02.005 23415702 · DOI
  81. [102]Allen J Romay-Tallon R Brymer KJ Caruncho HJ Kalynchuk LE. Mitochondria and mood: mitochondrial dysfunction as a key player in the manifestation of depression. Front Neurosci. (2018) 12: 386. 10.3389/fnins.2018.00386 29928190 PMC5997778 · DOI
  82. [103]Fattal O Link J Quinn K Cohen BH Franco K. Psychiatric comorbidity in 36 adults with mitochondrial cytopathies. CNS Spectr. (2007) 12: 429– 38. 10.1017/S1092852900015303 17545953 · DOI
  83. [104]Cataldo AM McPhie DL Lange NT Punzell S Elmiligy S Ye NZ. Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J Pathol. (2010) 177: 575– 85. 10.2353/ajpath.2010.081068 20566748 PMC2913344 · DOI
  84. [105]Petschner P Gonda X Baksa D Eszlari N Trivaks M Juhasz G. Genes linking mitochondrial function, cognitive impairment and depression are associated with endophenotypes serving precision medicine. Neuroscience (2018) 370: 207– 17. 10.1016/j.neuroscience.2017.09.049 28987512 · DOI
  85. [106]Woolley JD Khan BK Murthy NK Miller BL Rankin KP. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry (2011) 72: 126– 33. 10.4088/JCP.10m06382oli 21382304 PMC3076589 · DOI · Paper page
  86. [107]Galindo MF Ikuta I Zhu X Casadesus G Jordan J. Mitochondrial biology in Alzheimer's disease pathogenesis. J Neurochem. (2010) 114: 933– 45. 10.1111/j.1471-4159.2010.06814.x 20492350 · DOI
  87. [108]Henchcliffe C Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol. (2008) 4: 600– 9. 10.1038/ncpneuro0924 18978800 · DOI
  88. [109]Turner C Schapira AH. Mitochondrial matters of the brain: the role in Huntington's disease. J Bioenerg Biomembr. (2010) 42: 193– 8. 10.1007/s10863-010-9290-y 20480217 · DOI
  89. [110]Scaini G Santos PM Benedet J Rochi N Gomes LM Borges LS. Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants. Brain Res Bull. (2010) 82: 224– 7. 10.1016/j.brainresbull.2010.03.006 20347017 · DOI
  90. [111]Moretti A Gorini A Villa RF. Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry (2003) 8: 773– 85. 10.1038/sj.mp.4001353 12931205 · DOI
  91. [112]Martins-de-Souza D Guest PC Harris LW Vanattou-Saifoudine N Webster MJ Rahmoune H. Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients. Transl Psychiatry (2012) 2: e87. 10.1038/tp.2012.13 22832852 PMC3309534 · DOI
  92. [113]Kambe Y Miyata A. Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice. Neurosci Lett. (2015) 588: 166– 71. 10.1016/j.neulet.2015.01.006 25576703 · DOI
  93. [114]Gong Y Chai Y Ding JH Sun XL Hu G. Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain. Neurosci Lett. (2011) 488: 76– 80. 10.1016/j.neulet.2010.11.006 21070835 · DOI
  94. [115]Gamaro GD Streck EL Matte C Prediger ME Wyse AT Dalmaz C. Reduction of hippocampal Na+, K+-ATPase activity in rats subjected to an experimental model of depression. Neurochem Res. (2003) 28: 1339– 44. 10.1023/A:1024988113978 12938855 · DOI
  95. [116]Wen L Jin Y Li L Sun S Cheng S Zhang S. Exercise prevents raphe nucleus mitochondrial overactivity in a rat depression model. Physiol Behav. (2014) 132: 57– 65. 10.1016/j.physbeh.2014.04.050 24813829 · DOI
  96. [117]Chen C Wang Y Zhang J Ma L Gu J Ho G. Contribution of neural cell death to depressive phenotypes of streptozotocin-induced diabetic mice. Dis Models Mech. (2014) 7: 723– 30. 10.1242/dmm.016162 24764190 PMC4036479 · DOI
  97. [118]Norkett R Modi S Birsa N Atkin TA Ivankovic D Pathania M. DISC1-dependent regulation of mitochondrial dynamics controls the morphogenesis of complex neuronal dendrites. J Biol Chem. (2016) 291: 613– 29. 10.1074/jbc.M115.699447 26553875 PMC4705382 · DOI
  98. [119]Kato T. Molecular genetics of bipolar disorder and depression. Psychiatry Clin Neurosci. (2007) 61: 3– 19. 10.1111/j.1440-1819.2007.01604.x 17239033 · DOI
  99. [120]Urrutia PJ Mena NP Nunez MT. The interplay between iron accumulation, mitochondrial dysfunction, and inflammation during the execution step of neurodegenerative disorders. Front Pharmacol. (2014) 5: 38. 10.3389/fphar.2014.00038 24653700 PMC3948003 · DOI
  100. [121]Gardner A Boles RG. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuro Psychopharmacol Biol Psychiatry (2011) 35: 730– 43. 10.1016/j.pnpbp.2010.07.030 20691744 · DOI · Paper page
  101. [122]Cordeiro JL Marques W Hallak JE Osorio FL. Charcot-Marie-Tooth disease, psychiatric indicators and quality of life: a systematic review. ASN Neuro (2014) 6: 185– 92. 10.1042/AN20130048 24654889 PMC4034707 · DOI
  102. [123]Madrigal JL Olivenza R Moro MA Lizasoain I Lorenzo P Rodrigo J. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology (2001) 24: 420– 9. 10.1016/S0893-133X(00)00208-6 11182537 · DOI
  103. [124]Neitemeier S Jelinek A Laino V Hoffmann L Eisenbach I Eying R. BID links ferroptosis to mitochondrial cell death pathways. Redox Biol. (2017) 12: 558– 70. 10.1016/j.redox.2017.03.007 28384611 PMC5382034 · DOI
  104. [125]Jelinek A Heyder L Daude M Plessner M Krippner S Grosse R. Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radic Biol Med. (2018) 117: 45– 57. 10.1016/j.freeradbiomed.2018.01.019 29378335 · DOI
  105. [126]Grohm J Kim SW Mamrak U Tobaben S Cassidy-Stone A Nunnari J. Inhibition of Drp1 provides neuroprotection in vitro and in vivo. Cell Death Diff. (2012) 19: 1446– 58. 10.1038/cdd.2012.18 22388349 PMC3422469 · DOI
  106. [127]Ben-Shachar D Karry R. Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS ONE (2008) 3: e3676. 10.1371/journal.pone.0003676 18989376 PMC2579333 · DOI
  107. [128]Lee SH Ripke S Neale BM Faraone SV Purcell SM Perlis RH. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. (2013) 45: 984– 94. 10.1038/ng.2711 23933821 PMC3800159 · DOI · Paper page
  108. [129]Michels S Wohr M Schwarting RK Culmsee C. Psychiatric risk gene Cacna1c determines mitochondrial resilience against oxidative stress in neurons. Cell Death Dis. (2018) 9: 645. 10.1038/s41419-018-0676-9 29844355 PMC5974319 · DOI
  109. [130]Michels S Ganjam GK Martins H Schratt GM Wohr M Schwarting RKW. Downregulation of the psychiatric susceptibility gene Cacna1c promotes mitochondrial resilience to oxidative stress in neuronal cells. Cell Death Discov. (2018) 4: 54. 10.1038/s41420-018-0061-6 29760952 PMC5945680 · DOI
  110. [131]Kabir ZD Lee AS Burgdorf CE Fischer DK Rajadhyaksha AM Mok E. Cacna1c in the prefrontal cortex regulates depression-related behaviors via REDD1. Neuropsychopharmacology (2017) 42: 2032– 42. 10.1038/npp.2016.271 27922594 PMC5561335 · DOI
  111. [132]Yoshimizu T Pan JQ Mungenast AE Madison JM Su S Ketterman J Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons. Mol Psychiatry (2015) 20: 284 10.1038/mp.2014.181 25623946 · DOI · Paper page
  112. [134]Malkesman O Austin DR Tragon T Henter ID Reed JC Pellecchia M. Targeting the BH3-interacting domain death agonist to develop mechanistically unique antidepressants. Mol Psychiatry (2012) 17: 770– 80. 10.1038/mp.2011.77 21727899 PMC3274661 · DOI
  113. [135]Cardoso AL Costa P de Almeida LP Simoes S Plesnila N Culmsee C. Tf-lipoplex-mediated c-Jun silencing improves neuronal survival following excitotoxic damage in vivo. J Control. Release (2010) 142: 392– 403. 10.1016/j.jconrel.2009.11.004 19913061 · DOI
  114. [136]Culmsee C Plesnila N. Targeting Bid to prevent programmed cell death in neurons. Biochem Soc Trans. (2006) 34 (Pt 6): 1334– 40. 10.1042/BST0341334 17073814 · DOI
  115. [137]Pereira C Chavarria V Vian J Ashton MM Berk M Marx W. Mitochondrial agents for bipolar disorder. Int J Neuropsychopharmacol. (2018) 21: 550– 69. 10.1093/ijnp/pyy018 29596661 PMC6007750 · DOI
  116. [139]Zhu L Zhao Q Yang T Ding W Zhao Y. Cellular metabolism and macrophage functional polarization. Int Rev Immunol. (2015) 34: 82– 100. 10.3109/08830185.2014.969421 25340307 · DOI
  117. [141]Galvan-Pena S O'Neill LA. Metabolic reprograming in macrophage polarization. Front Immunol. (2014) 5: 420. 10.3389/fimmu.2014.00420 25228902 PMC4151090 · DOI · Paper page
  118. [142]Mills CD. M1 and M2 macrophages: oracles of health and disease. Crit Rev Immunol. (2012) 32: 463– 88. 10.1615/CritRevImmunol.v32.i6.10 23428224 · DOI
  119. [143]Rath M Muller I Kropf P Closs EI Munder M. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front Immunol. (2014) 5: 532. 10.3389/fimmu.2014.00532 25386178 PMC4209874 · DOI
  120. [144]De Santa F Vitiello L Torcinaro A Ferraro E. The role of metabolic remodeling in macrophage polarization and its effect on skeletal muscle regeneration. Antioxid Redox Signal. (2018). [Epub ahead of print]. 10.1089/ars.2017.742 30070144 · DOI
  121. [145]Klimaszewska-Lata J Gul-Hinc S Bielarczyk H Ronowska A Zysk M Gruzewska K. Differential effects of lipopolysaccharide on energy metabolism in murine microglial N9 and cholinergic SN56 neuronal cells. J Neurochem. (2015) 133: 284– 97. 10.1111/jnc.12979 25345568 · DOI
  122. [147]Van den Bossche J Baardman J de Winther MP Metabolic characterization of polarized M1 and M2 bone marrow-derived macrophages using real-time extracellular flux analysis. J Visual Exp. (2015) 105: e53424 10.3791/53424 PMC4692751 26649578 · DOI
  123. [150]Tyrrell DJ Bharadwaj MS Jorgensen MJ Register TC Shively C Andrews RN. Blood-based bioenergetic profiling reflects differences in brain bioenergetics and metabolism. Oxid Med Cell Longevity (2017) 2017: 7317251. 10.1155/2017/7317251 29098063 PMC5643153 · DOI
  124. [151]Prabakaran S Swatton JE Ryan MM Huffaker SJ Huang JT Griffin JL. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry (2004) 9: 684– 97, 643. 10.1038/sj.mp.4001511 15098003 · DOI
  125. [152]Karabatsiakis A Bock C Salinas-Manrique J Kolassa S Calzia E Dietrich DE. Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. Transl Psychiatry (2014) 4: e397. 10.1038/tp.2014.44 26126180 PMC4080325 · DOI
  126. [153]Hroudova J Fisar Z Kitzlerova E Zverova M Raboch J. Mitochondrial respiration in blood platelets of depressive patients. Mitochondrion (2013) 13: 795– 800. 10.1016/j.mito.2013.05.005 23688905 · DOI
  127. [154]Gubert C Stertz L Pfaffenseller B Panizzutti BS Rezin GT Massuda R. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects. J Psychiatr Res. (2013) 47: 1396– 402. 10.1016/j.jpsychires.2013.06.018 23870796 · DOI
  128. [155]Lopez-Armada MJ Riveiro-Naveira RR Vaamonde-Garcia C Valcarcel-Ares MN. Mitochondrial dysfunction and the inflammatory response. Mitochondrion (2013) 13: 106– 18. 10.1016/j.mito.2013.01.003 23333405 · DOI
  129. [156]Ng DS Chu T Esposito B Hui P Connelly PW Gross PL. Paraoxonase-1 deficiency in mice predisposes to vascular inflammation, oxidative stress, and thrombogenicity in the absence of hyperlipidemia. Cardiovasc Pathol. (2008) 17: 226– 32. 10.1016/j.carpath.2007.10.001 18402813 · DOI
  130. [157]Chacko BK Kramer PA Ravi S Benavides GA Mitchell T Dranka BP. The Bioenergetic Health Index: a new concept in mitochondrial translational research. Clin Sci. (2014) 127: 367– 73. 10.1042/CS20140101 24895057 PMC4202728 · DOI
  131. [158]Chacko BK Zhi D Darley-Usmar VM Mitchell T. The Bioenergetic Health Index is a sensitive measure of oxidative stress in human monocytes. Redox Biol. (2016) 8: 43– 50. 10.1016/j.redox.2015.12.008 26748041 PMC4712317 · DOI

Cited by

Sorted by citations

Authors
Culmsee, C., Michels, S., Scheu, S., Arolt, V., Dannlowski, U., & Alferink, J.
Affiliations
  • Philipps University of Marburg (DE)
  • Heinrich Heine University Düsseldorf (DE)
  • University of Münster (DE)
Corresponding author
  • Culmsee, Carsten
  • Alferink, Judith
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2019-01-09
Volume
9
Pages
739-739
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2018.00739
PMC
PMC6333629
OpenAlex
W2908587128
Cited by
110
References
27
Citations by year
2026: 13 · 2025: 14 · 2024: 14 · 2023: 16 · 2022: 10 · 2021: 15 · 2020: 18 · 2019: 10
FWCI
0.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft (FOR2107 (CU 43/9-1; CU43/9-2 to CC), FOR2107 (DA 1151/5-1; DA 1151/5-2 to UD), FOR2107 (AL 1145/5-2 to JA), RTG 2158 to SS, SFB-TRR58 (Projects C09 and Z02) to UD, EXC 1003 (grant: FF-2014-01) to JA)
  • European Commission
  • Alzheimer Forschung Initiative (14835)
  • Jürgen Manchot Stiftung
  • Bundesministerium für Bildung und Forschung (754740)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
major depressive disorder, mitochondria, microglia, neuroinflammation, inflammatory cytokines, innate immunity, immunometabolism, mitochondrial dysfunction, oxidative phosphorylation, reactive oxygen species, myeloid cells, microglial polarization, depression-like behavior, redox homeostasis, calcium homeostasis

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