Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Effects of Combined Treatments of Lithium and Valproate on the Phosphorylation of ERK1/2 and Transcriptional Activity of ELK1 and C-FOS in PC12 Cells

리튬 및 발프로에이트 병용 처치가 PC12 세포에서 ERK1/2 인산화와 ELK1 및 C-FOS 전사활성에 미치는 영향

  • Cha, Seung Keun (Department of Neuropsychiatry, Seoul National University Hospital) ;
  • Kim, Se Hyun (Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University) ;
  • Ha, Kyooseob (Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University) ;
  • Shin, Soon Young (Department of Biological Sciences, Konkuk University) ;
  • Kang, Ung Gu (Department of Neuropsychiatry, Seoul National University Hospital)
  • 차승근 (서울대학교병원 정신건강의학과) ;
  • 김세현 (서울대학교 의학연구원 인간행동의학연구소) ;
  • 하규섭 (서울대학교 의학연구원 인간행동의학연구소) ;
  • 신순영 (건국대학교 생명과학과) ;
  • 강웅구 (서울대학교병원 정신건강의학과)
  • Received : 2013.09.05
  • Accepted : 2013.09.17
  • Published : 2013.11.30
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Abstract

Objectives Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. Methods PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. Results Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. Conclusions Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.

Keywords

References

  1. Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet 2011;378:1306- 1315. https://doi.org/10.1016/S0140-6736(11)60873-8
  2. Cruz N, Sanchez-Moreno J, Torres F, Goikolea JM, Valentí M, Vieta E. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol 2010;13:5-14. https://doi.org/10.1017/S1461145709990344
  3. Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord 2013; 15:1-44.
  4. Goodwin GM; Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: revised second edition--recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2009;23: 346-348. https://doi.org/10.1177/0269881109102919
  5. Freeman MP, Stoll AL. Mood stabilizer combinations: a review of safety and efficacy. Am J Psychiatry 1998;155:12-21. https://doi.org/10.1176/ajp.155.1.12
  6. BALANCE investigators and collaborators, Geddes JR, Goodwin GM, Rendell J, Azorin JM, Cipriani A, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet 2010;375:385-395. https://doi.org/10.1016/S0140-6736(09)61828-6
  7. Chin PC, Majdzadeh N, D'Mello SR. Inhibition of GSK3beta is a common event in neuroprotection by different survival factors. Brain Res Mol Brain Res 2005;137:193-201. https://doi.org/10.1016/j.molbrainres.2005.03.004
  8. Machado-Vieira R, Manji HK, Zarate CA Jr. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 2009;11 Suppl 2:92-109. https://doi.org/10.1111/j.1399-5618.2009.00714.x
  9. De Sarno P, Li X, Jope RS. Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology 2002;43:1158-1164. https://doi.org/10.1016/S0028-3908(02)00215-0
  10. Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002;43: 1173-1179. https://doi.org/10.1016/S0028-3908(02)00217-4
  11. Nonaka S, Chuang DM. Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats. Neuroreport 1998;9:2081-2084. https://doi.org/10.1097/00001756-199806220-00031
  12. Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L, et al. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 2003;23:7311-7316.
  13. Yan XB, Hou HL, Wu LM, Liu J, Zhou JN. Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia. Neuropharmacology 2007;53:487-495. https://doi.org/10.1016/j.neuropharm.2007.06.020
  14. Kim AJ, Shi Y, Austin RC, Werstuck GH. Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 2005;118(Pt 1):89-99. https://doi.org/10.1242/jcs.01562
  15. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 2001;276: 36734-36741. https://doi.org/10.1074/jbc.M101287200
  16. Hao Y, Creson T, Zhang L, Li P, Du F, Yuan P, et al. Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis. J Neurosci 2004;24:6590-6599. https://doi.org/10.1523/JNEUROSCI.5747-03.2004
  17. Dou H, Ellison B, Bradley J, Kasiyanov A, Poluektova LY, Xiong H, et al. Neuroprotective mechanisms of lithium in murine human immunodeficiency virus-1 encephalitis. J Neurosci 2005;25:8375-8385. https://doi.org/10.1523/JNEUROSCI.2164-05.2005
  18. Kostrouchova M, Kostrouch Z, Kostrouchova M. Valproic acid, a molecular lead to multiple regulatory pathways. Folia Biol (Praha) 2007;53:37-49.
  19. Zhang Y, Sun Y, Wang F, Wang Z, Peng Y, Li R. Downregulating the canonical Wnt/$\beta$-catenin signaling pathway attenuates the susceptibility to autism-like phenotypes by decreasing oxidative stress. Neurochem Res 2012;37:1409-1419. https://doi.org/10.1007/s11064-012-0724-2
  20. Pardo R, Andreolotti AG, Ramos B, Picatoste F, Claro E. Opposed effects of lithium on the MEK-ERK pathway in neural cells: inhibition in astrocytes and stimulation in neurons by GSK3 independent mechanisms. J Neurochem 2003;87:417-426. https://doi.org/10.1046/j.1471-4159.2003.02015.x
  21. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002;298: 1911-1912. https://doi.org/10.1126/science.1072682
  22. English JD, Sweatt JD. Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J Biol Chem 1996;271: 24329-24332. https://doi.org/10.1074/jbc.271.40.24329
  23. Sweatt JD. Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol 2004;14:311-317. https://doi.org/10.1016/j.conb.2004.04.001
  24. Wu SP, Lu KT, Chang WC, Gean PW. Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation. J Biomed Sci 1999;6:409-417. https://doi.org/10.1007/BF02253672
  25. Goldin M, Segal M. Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons. Eur J Neurosci 2003;17:2529-2539. https://doi.org/10.1046/j.1460-9568.2003.02694.x
  26. Wu GY, Deisseroth K, Tsien RW. Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nat Neurosci 2001;4:151-158. https://doi.org/10.1038/83976
  27. Di Daniel E, Mudge AW, Maycox PR. Comparative analysis of the effects of four mood stabilizers in SH-SY5Y cells and in primary neurons. Bipolar Disord 2005;7:33-41.
  28. Kim SH, Seo MS, Jeon WJ, Yu HS, Park HG, Jung GA, et al. Haloperidol regulates the phosphorylation level of the MEK-ERKp90RSK signal pathway via protein phosphatase 2A in the rat frontal cortex. Int J Neuropsychopharmacol 2008;11:509-517.
  29. Pozzi L, Håkansson K, Usiello A, Borgkvist A, Lindskog M, Greengard P, et al. Opposite regulation by typical and atypical anti-psychotics of ERK1/2, CREB and Elk-1 phosphorylation in mouse dorsal striatum. J Neurochem 2003;86:451-459.
  30. Yuan PX, Huang LD, Jiang YM, Gutkind JS, Manji HK, Chen G. The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem 2001;276: 31674-31683. https://doi.org/10.1074/jbc.M104309200
  31. Dudbridge F. Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered 2008;66:87-98. https://doi.org/10.1159/000119108
  32. Yuan P, Zhou R, Wang Y, Li X, Li J, Chen G, et al. Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophrenia. J Affect Disord 2010;124:164-169. https://doi.org/10.1016/j.jad.2009.10.017
  33. Hsieh J, Nakashima K, Kuwabara T, Mejia E, Gage FH. Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci U S A 2004; 101:16659-16664. https://doi.org/10.1073/pnas.0407643101
  34. Michaelis M, Suhan T, Michaelis UR, Beek K, Rothweiler F, Tausch L, et al. Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells. Cell Death Differ 2006;13:446-453. https://doi.org/10.1038/sj.cdd.4401759
  35. Kopnisky KL, Chalecka-Franaszek E, Gonzalez-Zulueta M, Chuang DM. Chronic lithium treatment antagonizes glutamate-induced decrease of phosphorylated CREB in neurons via reducing protein phosphatase 1 and increasing MEK activities. Neuroscience 2003; 116:425-435. https://doi.org/10.1016/S0306-4522(02)00573-0
  36. Son H, Yu IT, Hwang SJ, Kim JS, Lee SH, Lee YS, et al. Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus. J Neurochem 2003;85:872-881. https://doi.org/10.1046/j.1471-4159.2003.01725.x
  37. Chen G, Manji HK. The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers. Curr Opin Psychiatry 2006;19:313-323. https://doi.org/10.1097/01.yco.0000218604.63463.cd
  38. Besnard A, Galan-Rodriguez B, Vanhoutte P, Caboche J. Elk-1 a transcription factor with multiple facets in the brain. Front Neurosci 2011;5:35.
  39. Ameyar M, Wisniewska M, Weitzman JB. A role for AP-1 in apoptosis: the case for and against. Biochimie 2003;85:747-752. https://doi.org/10.1016/j.biochi.2003.09.006
  40. Karin M, Liu Zg, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol 1997;9:240-246. https://doi.org/10.1016/S0955-0674(97)80068-3
  41. Brunello N, Tascedda F. Cellular mechanisms and second messengers: relevance to the psychopharmacology of bipolar disorders. Int J Neuropsychopharmacol 2003;6:181-189. https://doi.org/10.1017/S1461145703003419
  42. Asghari V, Wang JF, Reiach JS, Young LT. Differential effects of mood stabilizers on Fos/Jun proteins and AP-1 DNA binding activity in human neuroblastoma SH-SY5Y cells. Brain Res Mol Brain Res 1998; 58:95-102. https://doi.org/10.1016/S0169-328X(98)00107-7
  43. Atmaca M. Valproate and neuroprotective effects for bipolar disorder. Int Rev Psychiatry 2009;21:410-413. https://doi.org/10.1080/09540260902962206
  44. Atmaca M, Yildirim H, Ozdemir H, Ogur E, Tezcan E. Hippocampal 1H MRS in patients with bipolar disorder taking valproate versus valproate plus quetiapine. Psychol Med 2007;37:121-129. https://doi.org/10.1017/S0033291706008968
  45. Drevets WC. Neuroimaging studies of mood disorders. Biol Psychiatry 2000;48:813-829. https://doi.org/10.1016/S0006-3223(00)01020-9
  46. Chiu CT, Wang Z, Hunsberger JG, Chuang DM. Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder. Pharmacol Rev 2013;65:105-142. https://doi.org/10.1124/pr.111.005512
  47. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 2000;75:1729-1734.
  48. Laeng P, Pitts RL, Lemire AL, Drabik CE, Weiner A, Tang H, et al. The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells. J Neurochem 2004;91:238-251. https://doi.org/10.1111/j.1471-4159.2004.02725.x
  49. Bachmann RF, Schloesser RJ, Gould TD, Manji HK. Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeutics. Mol Neurobiol 2005;32: 173-202. https://doi.org/10.1385/MN:32:2:173
  50. McDonald C, Zanelli J, Rabe-Hesketh S, Ellison-Wright I, Sham P, Kalidindi S, et al. Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder. Biol Psychiatry 2004; 56:411-417. https://doi.org/10.1016/j.biopsych.2004.06.021
  51. Caetano SC, Olvera RL, Glahn D, Fonseca M, Pliszka S, Soares JC. Fronto-limbic brain abnormalities in juvenile onset bipolar disorder. Biol Psychiatry 2005;58:525-531. https://doi.org/10.1016/j.biopsych.2005.04.027
  52. Dickstein DP, Milham MP, Nugent AC, Drevets WC, Charney DS, Pine DS, et al. Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. Arch Gen Psychiatry 2005;62:734-741. https://doi.org/10.1001/archpsyc.62.7.734
  53. Selemon LD, Rajkowska G. Cellular pathology in the dorsolateral prefrontal cortex distinguishes schizophrenia from bipolar disorder. Curr Mol Med 2003;3:427-436. https://doi.org/10.2174/1566524033479663
  54. Drevets WC, Ongür D, Price JL. Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders. Mol Psychiatry 1998;3:220-226, 190- 191. https://doi.org/10.1038/sj.mp.4000370
  55. Todtenkopf MS, Vincent SL, Benes FM. A cross-study meta-analysis and three-dimensional comparison of cell counting in the anterior cingulate cortex of schizophrenic and bipolar brain. Schizophr Res 2005;73:79-89. https://doi.org/10.1016/j.schres.2004.08.018
  56. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-induced increase in human brain grey matter. Lancet 2000;356:1241- 1242. https://doi.org/10.1016/S0140-6736(00)02793-8
  57. Guidotti A, Dong E, Kundakovic M, Satta R, Grayson DR, Costa E. Characterization of the action of antipsychotic subtypes on valproate- induced chromatin remodeling. Trends Pharmacol Sci 2009;30: 55-60. https://doi.org/10.1016/j.tips.2008.10.010
  58. Machado-Vieira R, Ibrahim L, Zarate CA Jr. Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions. CNS Neurosci Ther 2011;17:699-704. https://doi.org/10.1111/j.1755-5949.2010.00203.x