신경아교세포와 기분장애

Neuroglia and Mood Disorder

  • 이정구 (인제대학교 해운대백병원 정신건강의학교실) ;
  • 서미경 (인제대학교 의과대학 백인제기념임상의학연구소 신경과학연구부) ;
  • 박성우 (인제대학교 의과대학 백인제기념임상의학연구소 신경과학연구부) ;
  • 김영훈 (인제대학교 해운대백병원 정신건강의학교실)
  • Lee, Jung Goo (Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Inje University) ;
  • Seo, Mi Kyong (Paik Institute for Clinical Research, Inje University) ;
  • Park, Sung Woo (Paik Institute for Clinical Research, Inje University) ;
  • Kim, Young Hoon (Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Inje University)
  • 투고 : 2015.04.13
  • 심사 : 2015.05.15
  • 발행 : 2015.05.31

초록

Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. A serious problem such as suicide is commonly occurring in the patients with depression. Till now, the monoamine hypothesis has been the most popular theory of pathogenesis for depression. However, the more specific pathophysiology of depression and cellular molecular mechanism underlying action of commercial antidepressants have not been clearly defined. Several recent studies demonstrated that glial cells, especially astrocytes, are a promising answer to the pathophysiology of depression. In this article, current understanding of biology and molecular mechanisms of glial cells in the pathology of mood disorder and new research on the pathophysiology of depression will be discussed.

키워드

참고문헌

  1. Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 2008;33: 88-109. https://doi.org/10.1038/sj.npp.1301574
  2. Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001;7:541-547. https://doi.org/10.1038/87865
  3. Massart R, Mongeau R, Lanfumey L. Beyond the monoaminergic hypothesis: neuroplasticity and epigenetic changes in a transgenic mouse model of depression. Philos Trans R Soc Lond B Biol Sci 2012;367:2485-2494. https://doi.org/10.1098/rstb.2012.0212
  4. Rajkowska G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 2000;48: 766-777. https://doi.org/10.1016/S0006-3223(00)00950-1
  5. Cotter D, Mackay D, Landau S, Kerwin R, Everall I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 2001;58:545-553. https://doi.org/10.1001/archpsyc.58.6.545
  6. Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A 1998; 95:13290-13295. https://doi.org/10.1073/pnas.95.22.13290
  7. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999;45: 1085-1098. https://doi.org/10.1016/S0006-3223(99)00041-4
  8. Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF, et al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 2000;5:142-149. https://doi.org/10.1038/sj.mp.4000696
  9. Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, et al. Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 2000;48:861-873. https://doi.org/10.1016/S0006-3223(00)00999-9
  10. Uranova NA, Vostrikov VM, Orlovskaya DD, Rachmanova VI. Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res 2004;67:269-275. https://doi.org/10.1016/S0920-9964(03)00181-6
  11. Vostrikov VM, Uranova NA, Orlovskaya DD. Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. Schizophr Res 2007;94:273-280. https://doi.org/10.1016/j.schres.2007.04.014
  12. Hamidi M, Drevets WC, Price JL. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 2004;55:563-569. https://doi.org/10.1016/j.biopsych.2003.11.006
  13. Smialowska M, Szewczyk B, Woźniak M, Wawrzak-Wlecial A, Domin H. Glial degeneration as a model of depression. Pharmacol Rep 2013;65:1572-1579. https://doi.org/10.1016/S1734-1140(13)71518-4
  14. Hashimoto K, Sawa A, Iyo M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 2007;62:1310-1316. https://doi.org/10.1016/j.biopsych.2007.03.017
  15. Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B. Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:70-75. https://doi.org/10.1016/j.pnpbp.2008.10.005
  16. Yang J, Shen J. In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine. Neuroscience 2005;135:927-937. https://doi.org/10.1016/j.neuroscience.2005.06.067
  17. Paul IA, Skolnick P. Glutamate and depression: clinical and preclinical studies. Ann N Y Acad Sci 2003;1003:250-272. https://doi.org/10.1196/annals.1300.016
  18. Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of de pression. Pharmacopsychiatry 1996;29:23-26. https://doi.org/10.1055/s-2007-979537
  19. Bunney BG, Bunney WE. Rapid-acting antidepressant strategies: mechanisms of action. Int J Neuropsychopharmacol 2012;15:695-713. https://doi.org/10.1017/S1461145711000927
  20. Largo C, Cuevas P, Somjen GG, Martin del Rio R, Herreras O. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival. J Neurosci 1996; 16:1219-1229. https://doi.org/10.1523/JNEUROSCI.16-03-01219.1996
  21. Nishiyama A, Komitova M, Suzuki R, Zhu X. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 2009;10:9-22.
  22. Swiss VA, Nguyen T, Dugas J, Ibrahim A, Barres B, Androulakis IP, et al. Identification of a gene regulatory network necessary for the initiation of oligodendrocyte differentiation. PLoS One 2011;6:e18088. https://doi.org/10.1371/journal.pone.0018088
  23. Buller B, Chopp M, Ueno Y, Zhang L, Zhang RL, Morris D, et al. Regulation of serum response factor by miRNA-200 and miRNA-9 modulates oligodendrocyte progenitor cell differentiation. Glia 2012; 60:1906-1914. https://doi.org/10.1002/glia.22406
  24. Rodnight RB, Gottfried C. Morphological plasticity of rodent astroglia. J Neurochem 2013;124:263-275. https://doi.org/10.1111/jnc.12087
  25. Wieronska JM, Pilc A. Metabotropic glutamate receptors in the tripartite synapse as a target for new psychotropic drugs. Neurochem Int 2009;55:85-97. https://doi.org/10.1016/j.neuint.2009.02.019
  26. Sanacora G, Banasr M. From pathophysiology to novel antidepressant drugs: glial contributions to the pathology and treatment of mood disorders. Biol Psychiatry 2013;73:1172-1179. https://doi.org/10.1016/j.biopsych.2013.03.032
  27. Gosselin RD, Gibney S, O'Malley D, Dinan TG, Cryan JF. Region specific decrease in glial fibrillary acidic protein immunoreactivity in the brain of a rat model of depression. Neuroscience 2009;159:915-925. https://doi.org/10.1016/j.neuroscience.2008.10.018
  28. Schroeter ML, Abdul-Khaliq H, Diefenbacher A, Blasig IE. S100B is increased in mood disorders and may be reduced by antidepressive treatment. Neuroreport 2002;13:1675-1678. https://doi.org/10.1097/00001756-200209160-00021
  29. Miguel-Hidalgo JJ, Rajkowska G. Comparison of prefrontal cell pathology between depression and alcohol dependence. J Psychiatr Res 2003;37:411-420. https://doi.org/10.1016/S0022-3956(03)00049-9
  30. Altshuler LL, Abulseoud OA, Foland-Ross L, Bartzokis G, Chang S, Mintz J, et al. Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder. Bipolar Disord 2010; 12:541-549. https://doi.org/10.1111/j.1399-5618.2010.00838.x
  31. Bowley MP, Drevets WC, Ongur D, Price JL. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 2002; 52:404-412. https://doi.org/10.1016/S0006-3223(02)01404-X
  32. Fatemi SH, Laurence JA, Araghi-Niknam M, Stary JM, Schulz SC, Lee S, et al. Glial fibrillary acidic protein is reduced in cerebellum of subjects with major depression, but not schizophrenia. Schizophr Res 2004;69:317-323. https://doi.org/10.1016/j.schres.2003.08.014
  33. John CS, Smith KL, Van't Veer A, Gompf HS, Carlezon WA Jr, Cohen BM, et al. Blockade of astrocytic glutamate uptake in the prefrontal cortex induces anhedonia. Neuropsychopharmacology 2012; 37:2467-2475. https://doi.org/10.1038/npp.2012.105
  34. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856-864. https://doi.org/10.1001/archpsyc.63.8.856
  35. Zadrożna M, Nowak B, Łason-Tyburkiewicz M, Wolak M, Sowa-Kucma M, Papp M, et al. Different pattern of changes in calcium binding proteins immunoreactivity in the medial prefrontal cortex of rats exposed to stress models of depression. Pharmacol Rep 2011; 63:1539-1546. https://doi.org/10.1016/S1734-1140(11)70718-6
  36. Sanacora G, Saricicek A. GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. CNS Neurol Disord Drug Targets 2007;6:127-140. https://doi.org/10.2174/187152707780363294
  37. Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, et al. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry 2010; 15:501-511. https://doi.org/10.1038/mp.2008.106
  38. Banasr M, Duman RS. Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 2008;64: 863-870. https://doi.org/10.1016/j.biopsych.2008.06.008
  39. Liu Q, Li B, Zhu HY, Wang YQ, Yu J, Wu GC. Clomipramine treatment reversed the glial pathology in a chronic unpredictable stressinduced rat model of depression. Eur Neuropsychopharmacol 2009; 19:796-805. https://doi.org/10.1016/j.euroneuro.2009.06.010
  40. Czeh B, Simon M, Schmelting B, Hiemke C, Fuchs E. Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment. Neuropsychopharmacology 2006;31:1616-1626. https://doi.org/10.1038/sj.npp.1300982
  41. Nichols NR, Osterburg HH, Masters JN, Millar SL, Finch CE. Messenger RNA for glial fibrillary acidic protein is decreased in rat brain following acute and chronic corticosterone treatment. Brain Res Mol Brain Res 1990;7:1-7. https://doi.org/10.1016/0169-328X(90)90066-M
  42. Rajkowska G, Stockmeier CA. Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr Drug Targets 2013;14:1225-1236. https://doi.org/10.2174/13894501113149990156
  43. Chaudhry FA, Lehre KP, van Lookeren Campagne M, Ottersen OP, Danbolt NC, Storm-Mathisen J. Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 1995;15: 711-720. https://doi.org/10.1016/0896-6273(95)90158-2
  44. Zink M, Vollmayr B, Gebicke-Haerter PJ, Henn FA. Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology 2010;58:465-473. https://doi.org/10.1016/j.neuropharm.2009.09.005
  45. Lee Y, Gaskins D, Anand A, Shekhar A. Glia mechanisms in mood regulation: a novel model of mood disorders. Psychopharmacology (Berl) 2007;191:55-65. https://doi.org/10.1007/s00213-006-0652-4
  46. Garcia LS, Comim CM, Valvassori SS, Reus GZ, Barbosa LM, Andreazza AC, et al. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:140-144. https://doi.org/10.1016/j.pnpbp.2007.07.027
  47. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010;329:959-964. https://doi.org/10.1126/science.1190287
  48. Duman RS, Malberg J, Thome J. Neural plasticity to stress and antidepressant treatment. Biol Psychiatry 1999;46:1181-1191. https://doi.org/10.1016/S0006-3223(99)00177-8
  49. Lee JG, Seo MK, Park SW, Baek JH, Kim YH. Understanding the molecular biology in the pathogenesis of depression. Korean J Psychopharmacol 2012;23:147-154.
  50. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci 2009;122(Pt 20):3589-3594. https://doi.org/10.1242/jcs.051011
  51. Jernigan CS, Goswami DB, Austin MC, Iyo AH, Chandran A, Stockmeier CA, et al. The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1774-1779. https://doi.org/10.1016/j.pnpbp.2011.05.010