우울장애의 신경생물학적 기전으로서 세포 내 신호전달계의 역할
The Role of Intracellular Signaling Pathways in the Neurobiology of the Depressive Disorder
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초록
Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.
Abstract
Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.
참고문헌 (94)
- Wong ML, "From monoamines to genomic targets: a paradigm shift for drug discovery in depression", Nat Rev Drug Discov, 3, pp.136~151 (2004)
- Diazgranados N, "A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression", Arch Gen Psychiatry, 67, pp.793~802 (2010)
- DiazGranados N, "Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder", J Clin Psychiatry, 71, pp.1605~1611 (2010)
- Li N, "mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists", Science, 329, pp.959~964 (2010)
- Autry AE, "NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses", Nature, 475, pp.91~95 (2011)[DOI]
- Duman RS, "A neurotrophic model for stress-related mood disorders", Biol Psychiatry, 59, pp.1116~1127 (2006)
- Manji HK, "Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics", Psychopharmacol Bull, 35, pp.5~49 (2001)
- Manji HK, "The cellular neurobiology of depression", Nat Med, 7, pp.541~547 (2001)
- Sheline YI, "Untreated depression and hippocampal volume loss", Am J Psychiatry, 160, pp.1516~1518 (2003)
- Vermetten E, "Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder", Biol Psychiatry, 54, pp.693~702 (2003)
- Czéh B, "Watanabe T, Frahm J, de Biurrun G, van Kampen M, et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine", Proc Natl Acad Sci U S A, 98, pp.12796~12801 (2001)
- Madsen TM, "Increased neurogenesis in a model of electroconvulsive therapy", Biol Psychiatry, 47, pp.1043~1049 (2000)
- Manev H, "Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro", Eur J Pharmacol, 411, pp.67~70 (2001)
- Santarelli L, "Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants", Science, 301, pp.805~809 (2003)
- Schmidt HD, "Future Antidepressant Targets: Neurotrophic Factors and Related Signaling Cascades", Drug Discov Today Ther Strateg, 5, pp.151~156 (2008)
- David DJ, "Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety", depression, 2009, pp.62, 479~493
- Bessa JM, "The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling", Mol Psychiatry, 14, pp.764~773 (2009)
- Adayev T, "Transmembrane signaling in the brain by serotonin, a key regulator of physiology and emotion", Biosci Rep, 25, pp.363~385 (2005)
- Zheng M, "Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling", Pharmacol Ther, 108, pp.257~268 (2005)
- Aantaa R, "Molecular pharmacology of alpha 2-adrenoceptor subtypes", Ann Med, 27, pp.439~449 (1995)
- Kamenetsky M, "Molecular details of cAMP generation in mammalian cells: a tale of two systems", J Mol Biol, 362, pp.623~639 (2006)
- Dowlatshahi D, "Increased temporal cortex CREB concentrations and antidepressant treatment in major depression", Lancet, 352, pp.1754~1755 (1998)
- Dowlatshahi D, "G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death", J Neurochem, 73, pp.1121~1126 (1999)
- Cowburn RF, "Adenylyl cyclase activity and G-protein subunit levels in postmortem frontal cortex of suicide victims", Brain Res, 633, pp.297~304 (1994)
- Manier DH, "Beta-adrenoceptorlinked protein kinase A (PKA) activity in human fibroblasts from normal subjects and from patients with major depression", Neuropsychopharmacology, 15, pp.555~561 (1996)
- Manier DH, "Human fibroblasts as a relevant model to study signal transduction in affective disorders", J Affect Disord, 61, pp.51~58 (2000)
- Perez J, "cAMP-dependent phosphorylation of soluble and crude microtubule fractions of rat cerebral cortex after prolonged desmethylimipramine treatment", Eur J Pharmacol, 172, pp.305~316 (1989)
- Nestler EJ, "Chronic antidepressant administration alters the subcellular distribution of cyclic AMP-dependent protein kinase in rat frontal cortex", J Neurochem, 53, pp.1644~1647 (1989)
- Nibuya M, "Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus", J Neurosci, 16, pp.2365~2372 (1996)
- Fujimaki K, "Administration of a cAMP phosphodiesterase 4 inhibitor enhances antidepressant-induction of BDNF mRNA in rat hippocampus", Neuropsychopharmacology, 22, pp.42~51 (2000)
- Jeon SH, "Electroconvulsive shock increases the phosphorylation of cyclic AMP response element binding protein at Ser-133 in rat hippocampus but not in cerebellum", Neuropharmacology, 36, pp.411~414 (1997)
- Thome J, "cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment", J Neurosci, 20, pp.4030~4036 (2000)
- Deogracias R, "Expression of the neurotrophin receptor trkB is regulated by the cAMP", CREB pathway in neurons, 2004, pp.26, 470~480
- Fukuchi M, "Transcriptional regulation of neuronal genes and its effect on neural functions: cumulative mRNA expression of PACAP and BDNF genes controlled by calcium and cAMP signals in neurons", J Pharmacol Sci, 98, pp.212~218 (2005)
- McCauslin CS, "CAAT", enhancer-binding protein delta and cAMP-response element- binding protein mediate inducible expression of the nerve growth factor gene in the central nervous system, 2006, pp.281, 17681~17688
- Chen AC, "Expression of the cAMP response element binding protein (CREB) in hippocampus produces an antidepressant effect", Biol Psychiatry, 49, pp.753~762 (2001)
- Newton SS, "Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressantlike effect", J Neurosci, 22, pp.10883~10890 (2002)
- Pliakas AM, "Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element- binding protein expression in nucleus accumbens", J Neurosci, 21, pp.7397~7403 (2001)
- Tanis KQ, "CREB binding and activity in brain: regional specificity and induction by electroconvulsive seizure", Biol Psychiatry, 63, pp.710~720 (2008)
- Johnson GL, "Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases", Science, 298, pp.1911~1912 (2002)
- Sweatt JD, "Mitogen-activated protein kinases in synaptic plasticity and memory", Curr Opin Neurobiol, 14, pp.311~317 (2004)
- Wu GY, "Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology", Nat Neu rosci, 4, pp.151~158 (2001)
- Roux PP, "ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions", Microbiol Mol Biol Rev, 68, pp.320~344 (2004)
- Dwivedi Y, "ERK MAP kinase signaling in post-mortem brain of suicide subjects: differential regulation of upstream Raf kinases Raf-1 and B-Raf", Mol Psychiatry, 11, pp.86~98 (2006)
- Dwivedi Y, "Reduced activation and expression of ERK1", 2 MAP kinase in the post-mortem brain of depressed suicide subjects, 2001, pp.77, 916~928
- Karege F, "Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs", Brain Res Mol Brain Res, 136, pp.29~37 (2005)
- Mercier G, "MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes", J Mol Neurosci, 24, pp.207~216 (2004)
- Kodama M, "Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain", Neuropsychopharmacology, 30, pp.360~371 (2005)
- Bhat RV, "Region-specific targets of p42", p44MAPK signaling in rat brain, 1998, pp.70, 558~571
- Kang UG, "Activation of extracellular signal-regulated kinase signaling by chronic electroconvulsive shock in the rat frontal cortex", Psychiatry Res, 145, pp.75~78 (2006)
- Gourley SL, "Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression", Biol Psychiatry, 63, pp.353~359 (2008)
- Duman CH, "A role for MAP kinase signaling in behavioral models of depression and antidepressant treatment", Biol Psychiatry, 61, pp.661~670 (2007)
- Einat H, "The role of the extracellular signal-regulated kinase signaling pathway in mood modulation", J Neurosci, 23, pp.7311~7316 (2003)
- Dwivedi Y, "Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects", Arch Gen Psychiatry, 60, pp.804~515 (2003)
- Karege F, "Decreased serum brain-derived neurotrophic factor levels in major depressed patients", Psychiatry Res, 109, pp.143~148 (2002)
- Shimizu E, "Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants", Biol Psychiatry, 54, pp.70~75 (2003)
- Evans SJ, "Dysregulation of the fibroblast growth factor system in major depression", Proc Natl Acad Sci U S A, 101, pp.15506~15511 (2004)
- Ueyama T, "Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain", Neurosci Res, 28, pp.103~110 (1997)
- Heine VM, "Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression", Eur J Neurosci, 21, pp.1304~1314 (2005)
- Gonul AS, "Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients", Eur Arch Psychiatry Clin Neurosci, 255, pp.381~386 (2005)
- Chen B, "Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication", Biol Psychiatry, 50, pp.260~265 (2001)
- Aydemir O, "The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study", Prog Neuropsychopharmacol Biol Psychiatry, 29, pp.261~265 (2005)
- Gervasoni N, "Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode", Neuropsychobiology, 51, pp.234~238 (2005)
- Schmidt HD, "Peripheral BDNF produces antidepressant- like effects in cellular and behavioral models", Neuropsychopharmacology, 35, pp.2378~2391 (2010)
- Shirayama Y, "Brainderived neurotrophic factor produces antidepressant effects in behavioral models of depression", J Neurosci, 22, pp.3251~3261 (2002)
- Murphy LO, "MAPK signal specificity: the right place at the right time", Trends Biochem Sci, 31, pp.268~275 (2006)
- Jeon SH, "MKP-1 induced in rat brain after electroconvulsive shock is independentof regulation of 42- and 44-kDa MAPK activity", Biochem BiophysRes Commun, 249, pp.692~696 (1998)
- Duric V, "A negative regulator of MAP kinase causes depressive behavior", Nat Med, 16, pp.1328~1332 (2010)
- Fayard E, "Protein kinase B", Akt at a glance, 2005, pp.118, 5675~5678
- Beaulieu JM, "An Akt", beta-arrestin 2, Cell, pp.2005, 122[DOI]
- Beaulieu JM, "Lithium antagonizes dopamine-dependent behaviors mediated by an AKT", glycogen synthase kinase 3 signaling cascade, 2004, pp.101, 5099~5104
- Kang UG, "Activation of protein kinase B (Akt) signaling after electroconvulsive shock in the rat hippocampus", Prog Neuropsychopharmacol Biol Psychiatry, 28, pp.41~44 (2004)
- Krishnan V, "AKT signaling within the ventral tegmental area regulates cellular and behavioral responses to stressful stimuli", Biol Psychiatry, 64, pp.691~700 (2008)
- Polter A, "Forkhead box, class O transcription factors in brain: regulation and behavioral manifestation", Biol Psychiatry, 65, pp.150~159 (2009)
- Yu HS, "Activation of Akt signaling in rat brain by intracerebroventricular injection of ouabain: a rat model for mania", Prog Neuropsychopharmacol Biol Psychiatry, 34, pp.888~894 (2010)
- Grimes CA, "The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling", Prog Neurobiol, 65, pp.391~426 (2001)
- Klein PS, "A molecular mechanism for the effect of lithium on development", Proc Natl Acad Sci U S A, 93, pp.8455~8459 (1996)
- Stambolic V, "Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells", Curr Biol, 6, pp.1664~1668 (1996)
- Roh MS, "Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: protection by mood stabilizers and imipramine", Biol Psychiatry, 57, pp.278~286 (2005)
- Li X, "In vivo regulation of glycogen synthase kinase-3beta (GSK3beta) by serotonergic activity in mouse brain", Neuropsychopharmacology, 29, pp.1426~1431 (2004)
- Madsen TM, "Chronic electroconvulsive seizure up-regulates beta-catenin expression in rat hippocampus: role in adult neurogenesis", Biol Psychiatry, 54, pp.1006~1014 (2003)
- Roh MS, "Biphasic changes in the Ser-9 phosphorylation of glycogen synthase kinase-3beta after electroconvulsive shock in the rat brain", Prog Neuropsychopharmacol Biol Psychiatry, 27, pp.1~5 (2003)
- Okamoto H, "Wnt2 expression and signaling is increased by different classes of antidepressant treatments", Biol Psychiatry, 68, pp.521~527 (2010)
- Kaidanovich-Beilin O, "Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus", Biol Psychiatry, 55, pp.781~784 (2004)
- Gould TD, "AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swimtest", Int J Neuropsychopharmacol, 7, pp.387~390 (2004)
- Costa-Mattioli M, "Translational control of long-lasting synaptic plasticity and memory", Neuron, 61, pp.10~26 (2009)
- Proud CG, "Signalling to translation: how signal transduction pathways control the protein synthetic machinery", Biochem J, 403, pp.217~234 (2007)
- Lehman JA, "Molecular crosstalk between p70S6k and MAPK cell signaling pathways", Biochem Biophys Res Commun, 293, pp.463~469 (2002)
- Roux PP, "RAS", ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation, 2007, pp.282, 14056~14064
- Farber NB, "The NMDA receptor hypofunction model of psychosis", Ann N Y Acad Sci, 1003, pp.119~130 (2003)
- Thomas DM, "MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity", Brain Res, 1050, pp.190~198 (2005)
- Papp M, "Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression", Eur J Pharmacol, 263, pp.1~7 (1994)
- Li N, "Glutamate Nmethyl- D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure", Biol Psychiatry, 69, pp.754~761 (2011)
- Jernigan CS, "The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder", Prog Neuropsychopharmacol Biol Psychiatry, 35, pp.1774~1779 (2011)
