Increases in iPS Transcription Factor (Oct4, Sox2, c-Myc, and Klf4) Gene Expression after Modified Electroconvulsive Therapy
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
ObjectiveaaElectroconvulsive therapy (ECT) is a reasonable option for intractable depression or schizophrenia, but a mechanism of action has not been established. One credible hypothesis is related to neural plasticity. Three genes (Oct4, Sox2, c-Myc) involved in the induction of induced pluripotent stem (iPS) cells are Wnt-target genes, which constitute a key gene group involved in neural plasticity through the TCF family. Klf4 is the other gene among Yamanaka’s four transcription factors, and increases in its expression are induced by stimulation of the canonical Wnt pathway. MethodsaaWe compared the peripheral blood gene expression of the four iPS genes (Oct4, Sox2, c-Myc, and Klf4) before and after modified ECT (specifically ECT with general anesthesia) of patients with intractable depression (n=6) or schizophrenia (n=6). Using Thymatron ten times the total bilateral electrical stimulation was evoked. ResultsaaBoth assessments of the symptoms demonstrated significant improvement after mECT stimulation. Expression of all four genes was confirmed to increase after initial stimulation. The gene expression levels after treatment were significantly different from the initial gene expression in all twelve cases at the following treatment stages: at the 3rd mECT for Oct4; at the 6th and 10th mECT for Sox2; and at the 3rd, 6th and 10th mECT for c-Myc. ConclusionaaThese significant differences were not present after correction for multiple testing; however, our data have the potential to explain the molecular mechanisms of mECT from a unique perspective. Further studie should be conducted to clarify the pathophysiological involvement of iPS-inducing genes in ECT.
Abstract
ObjectiveaaElectroconvulsive therapy (ECT) is a reasonable option for intractable depression or schizophrenia, but a mechanism of action has not been established. One credible hypothesis is related to neural plasticity. Three genes (Oct4, Sox2, c-Myc) involved in the induction of induced pluripotent stem (iPS) cells are Wnt-target genes, which constitute a key gene group involved in neural plasticity through the TCF family. Klf4 is the other gene among Yamanaka’s four transcription factors, and increases in its expression are induced by stimulation of the canonical Wnt pathway. MethodsaaWe compared the peripheral blood gene expression of the four iPS genes (Oct4, Sox2, c-Myc, and Klf4) before and after modified ECT (specifically ECT with general anesthesia) of patients with intractable depression (n=6) or schizophrenia (n=6). Using Thymatron ten times the total bilateral electrical stimulation was evoked. ResultsaaBoth assessments of the symptoms demonstrated significant improvement after mECT stimulation. Expression of all four genes was confirmed to increase after initial stimulation. The gene expression levels after treatment were significantly different from the initial gene expression in all twelve cases at the following treatment stages: at the 3rd mECT for Oct4; at the 6th and 10th mECT for Sox2; and at the 3rd, 6th and 10th mECT for c-Myc. ConclusionaaThese significant differences were not present after correction for multiple testing; however, our data have the potential to explain the molecular mechanisms of mECT from a unique perspective. Further studie should be conducted to clarify the pathophysiological involvement of iPS-inducing genes in ECT.
참고문헌 (35)
- Lisanby SH, "Electroconvulsive therapy for depression", N Engl J Med, 357, pp.1939~1945 (2007)
- Kellner CH, "ECT in treatment-resistant depression", Am J Psychiatry, 169, pp.1238~1244 (2012)
- Zervas IM, "Using ECT in schizophrenia: a review from a clinical perspective", World J Biol Psychiatry, 13, pp.96~105 (2012)
- Pompili M, "Indications for electroconvulsive treatment in schizophrenia: a systematic review", Schizophr Res, 146, pp.1~9 (2013)
- Bolwig TG, "How does electroconvulsive therapy work? Theories on its mechanism", Can J Psychiatry, 56, pp.13~18 (2011)
- Fochtmann LJ, "Genetic approaches to the neurobiology of electroconvulsive therapy", J ECT, 14, pp.206~219 (1998)
- Salter MW, "Src kinases: a hub for NMDA receptor regulation", Nat Rev Neurosci, 5, pp.317~328 (2004)
- Andrade C, "Possible glutamatergic and lipid signalling mechanisms in ECT-induced retrograde amnesia: experimental evidence for involvement of COX-2, and review of literature", J Psychiatr Res, 42, pp.837~850 (2008)
- Naylor P, "Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus", Brain Res Mol Brain Res, 35, pp.349~353 (1996)
- Bliss TV, "Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path", J Physiol, 232, pp.331~356 (1973)
- Andersen P, "A prelude to long-term potentiation", Philos Trans R Soc Lond B Biol Sci, 358, pp.613~615 (2003)
- Lynch MA, "Long-term potentiation and memory", Physiol Rev, 84, pp.87~136 (2004)
- Cooke SF, "Plasticity in the human central nervous system", Brain, 129, pp.1659~1673 (2006)
- Bear MF, "Synaptic plasticity: LTP and LTD", Curr Opin Neurobiol, 4, pp.389~399 (1994)
- Malenka RC, "LTP and LTD: an embarrassment of riches", Neuron, 44, pp.5~21 (2004)
- Li W, "Effects of electroconvulsive stimulation on long-term potentiation and synaptophysin in the hippocampus of rats with depressive behavior", J ECT, 28, pp.111~117 (2012)
- Kemler R, "From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion", Trends Genet, 9, pp.317~321 (1993)
- Vleminckx K, "The C-terminal transactivation domain of beta-catenin is necessary and sufficient for signaling by the LEF-1", beta-catenin complex in Xenopus laevis, 1999, pp.81, 65~74
- MacDonald BT, "Wnt", beta-catenin signaling: components, mechanisms, and diseases, 2009, pp.17, 9~26
- Logan CY, "The Wnt signaling pathway in development and disease", Annu Rev Cell Dev Biol, 20, pp.781~810 (2004)
- Komiya Y, "Wnt signal transduction pathways", Organogenesis, 4, pp.68~75 (2008)
- "The wnt homepage"[URL]
- Takahashi K, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell, 126, pp.663~676 (2006)
- Okita K, "Generation of germline-competent induced pluripotent stem cells", Nature, 448, pp.313~317 (2007)
- Takahashi K, "Induction of pluripotent stem cells from adult human fibroblasts by defined factors", Cell, 131, pp.861~872 (2007)
- Niwa H, "A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells", Nature, 460, pp.118~122 (2009)
- American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders, Text Revision (DSM-IV-TR)" (2000), American Psychiatric Association
- Kay SR, "The positive and negative syndrome scale (PANSS) for schizophrenia", Schizophr Bull, 13, pp.261~276 (1987)
- Hedlund JL, "HRSD-21: The Hamilton Rating Scale for Depression", J Oper Psychiatry, 10, pp.149~165 (1979)
- Petrides G, "The “half-age” stimulation strategy for ECT dosing", Convuls Ther, 12, pp.138~146 (1996)
- Nakatake Y, "Klf4 cooperates with Oct3", 4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells, 2006, pp.26, 7772~7782
- Ma DK, "Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis", Science, 323, pp.1074~1077 (2009)
- Chaturvedi S, "Effect of electroconvulsive therapy on hematological parameters", Psychiatry Res, 104, pp.265~268 (2001)
- Kronfol Z, "Acute effects of electroconvulsive therapy on lymphocyte natural killer cell activity in patients with major depression", J Affect Disord, 71, pp.211~215 (2002)
- Yang S, "Modulating the differentiation status of ex vivo-cultured anti-tumor T cells using cytokine cocktails", Cancer Immunol Immunother, 62, pp.727~736 (2013)