ROLE OF ENZYMES IN THE PATHOGENESIS OF DEPRESSION


Vaibhav Walia

Abstract


Depression is one of the most prevalent neuropsychiatric disorders that occurs due to the alterations in the monoaminergic system of the body. Various factors may be responsible for the alterations in the monoaminergic system. MAO-A is an enzyme which metabolizes the monoamines and thus responsible for the reduction in the level of monoamines in the body. Stress induces the increase expression and levels of various proinflammatory cytokines such as IL-6, IL-1β, TNF-α and PGE2 involved in the pathogenesis of depression. These proinflammatory cytokines increase or decrease the activity of various enzymes that further led to the reduction in the serotonin level of the brain. Thus, it has been suggested that the depression which is considered as a disorder that arises due to the imbalance in the neurotransmitters in the brain arises due to the alterations in the activities of the various enzymes. Therefore the aim of present review is to demonstrate the role of the various enzymes in the pathogenesis of depression.

Keywords: Depression, Enzymes, Nitric oxide, Stress.


| PDF | HTML |

References


Dannehl K, Rief W, Schwarz MJ. The predictive value of somatic and cognitive depressive symptoms for cytokine changes in patients with major depression. Neuropsychiatr Dis Treat 2014;10:1191-7.

Donato F, de Gomes MG, Goes AT. Involvement of the dopaminergic and serotonergic systems in the antidepressant-like effect caused by 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole. Life Sci 2013;93:393-400.

Voinov B, Richie WD, Bailey RK. Depression and chronic diseases: it is time for a synergistic mental health and primary care approach. Prim Care Comp CNS Dis 2013;15: PCC.12r01468. Doi: 10.4088/PCC.12r01468. [Article in Press]

Rao U. Biomarkers in pediatric depression. Depression Anxiety 2013;30:787-91.

Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bul 2014;140:774-815.

Cito MC, Silva MI, Santos LK. Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for the involvement of the monoaminergic system. Braz J Med Biol Res 2015;48:57-64.

Zeni AL, Zomkowski AD, Maraschin M. Evidence of the involvement of the monoaminergic systems in the antidepressant-like effect of Aloysia gratissima. J Ethnopharmacol 2013;148:914-20.

Berk M, Dean O, Drexhage H. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med 2013;11:74.

Penn E, Tracy DK. The drugs don’t work? antidepressants and the current and future pharmacological management of depression. Ther Adv Psychopharmacol 2012;2:179-88.

Hurley LL, Tizabi Y. Neuroinflammation, neurodegeneration, and depression. Neurotoxic Res 2013;23:131-44.

Rawdin BJ, Mellon SH, Dhabhar FS. Dysregulated relationship of inflammation and oxidative stress in major depression. Brain Behav Immunol 2013;31:143-52.

Maletic V, Raison C. Integrated neurobiology of bipolar disorder. Front Psychiatry 2014;5:98.

Numakawa T, Richards M, Nakajima S. The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition. Front Psychiatry 2014;5:136.

Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep 2011;13:467-75.

Fields C, Drye L, Vaidya V. Celecoxib or naproxen treatment does not benefit depressive symptoms in persons aged 70 and over: findings from a randomized controlled trial. Am J Ger Psychiatry 2012;20:505-13.

Müller N, Myint AM, Schwarz MJ. The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders--relation to drug treatment. Dialogues Clin Neurosci 2009;11:319-32.

Shelton RC, Miller AH. Inflammation in depression: is adiposity a cause? Dialogues Clin Neurosci 2011;13:41-53.

Weinberger JF, Raison CL, Rye DB. Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment-resistant depression and high inflammation. Brain Behav Immun 2015;47:193-200.

Cooke EL, Uings IJ, Xia CL. Functional analysis of the interleukin-1-receptor-associated kinase (IRAK-1) in interleukin-1 beta-stimulated nuclear factor kappa B (NF-kappa B) pathway activation: IRAK-1 associated with the NF-kappa B essential modulator (NEMO) upon receptor stimulation. Biochem J 2001;359:403-10.

Hua Y, Huang XY, Zhou L. DETA/NONO ate, a nitric oxide donor, produces antidepressant effects by promoting hippocampal neurogenesis. Psychopharmacol 2008;200:231-42.

Alexopoulos GS, Morimoto SS. The inflammation hypothesis in geriatric depression. Int J Geriatric Psychiatry 2011;26:1109-18.

Garry PS, Ezra M, Rowland MJ. The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol 2015;263:235-43.

Liu Y, Li W, Hu L. Downregulation of nitric oxide by electroacupuncture against hypoxic-ischemic brain damage in rats via nuclear factor-κB/neuronal nitric oxide synthase. Mol Med Rep 2015;11:837-42.

Byun JS, Lee SH, Jeon SH. Kainic acid-induced neuronal death is attenuated by aminoguanidine but aggravated by L-NAME in mouse hippocampus. Korean J Physiol Pharmacol 2009;13:265-71.

Cheah JH, Kim SF, Hester LD. DA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase dexras1. Neuron 2006;51:431-40.

Qiu Z, Parsons KL, Gruol DL. Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons. J Neurosci 1995;75:6686-99.

Villalba N, Sonkusare SK, Longden TA. Traumatic brain injury disrupts cerebrovascular tone through endothelial inducible nitric oxide synthase expression and nitric oxide gain of function. J Am Heart Ass: Cardiovascular Cerebrovascular Dis 2014;3:e001474. Doi:10.1161/JAHA.114.001474. [Article in Press]

Hu J, Ma S, Zou S. The regulation of nitric oxide synthase isoform expression in mouse and human fallopian tubes: potential insights for ectopic pregnancy. Int J Mol Sci 2015;16:49-67.

Liu HT, Mu DZ. Inducible nitric oxide synthase and brain hypoxic-ischemic brain damage. Chin J Contemp Pediat 2014;16:962-7.

Farhad AR, Razavi SM, Nejad PA. The use of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to evaluate the role of nitric oxide on periapical healing. Dent Res J 2011;8:197-202.

Malaviya R, Venosa A, Hall L. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor. Toxicol Appl Pharmacol 2012;265:279-91.

Canpolat S, Kırpınar I, Deveci E. Relationship of asymmetrical dimethylarginine, nitric oxide, and sustained attention during an attack in patients with the major depressive disorder. Sci World J 2014;2014:624395. Doi:10.1155/2014/624395. [Article in Press]

Talarowska M, Bobińska K, Zajączkowska M. Impact of oxidative/nitrosative stress and inflammation on cognitive functions in patients with recurrent depressive disorders. Med Sci Monit 2014;20:110-5.

Freitas AE, Moretti M, Budni J. NMDA receptors and the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway are implicated in the antidepressant-like action of the ethanolic extract from Tabebuia avellanedae in mice. J Med Food 2013;16:1030-8.

Soliman M. Preservation of myocar dialogues contractile function by aminoguanidine, a nitric oxide synthase inhibitors, in a rat model of hemorrhagic shock. Pak J Med Sci 2013;29:1415-9.

Vargas HO, Nunes SO, de Castro MR. Oxidative stress and inflammatory markers are associated with depression and nicotine dependence. Neurosci Lett 2013;544:136-40.

Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med 2015;13:68.

Villégier AS, Gallager B, Heston J. Age influences the effects of nicotine and monoamine oxidase inhibition on mood-related behaviors in rats. Psychopharmacol (Berl). 2010;208:593-601.

Wimbiscus M, Kostenko O, Malone D. MAO inhibitors: risks, benefits, and lore. Cleveland Clin J Med 2010;77:859-82.

Crisafulli C, Fabbri C, Porcelli S. Pharmacogenetics of antidepressants. Front Pharmacol 2011;16;2:6.

Chaurasiya ND, Ibrahim MA, Muhammad I. Monoamine oxidase inhibitory constituents of propolis: kinetics and mechanism of inhibition of recombinant human MAO-A and MAO-B. Molecules 2014;19:18936-52.

Sacher J, Houle S, Parkes J. Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: an [11C]-harmine PET study. J Psychiatry Neurosci 2011;36:375-82.

Mallinger AG, Frank E, Thase ME. Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior? Psychopharmacol Bull 2009;42:64-74.

Kitaichi Y, Inoue T, Mitsui N. Selegiline remarkably improved stage 5 treatment-resistant major depressive disorder: a case report. Neuropsychiatr Dis Treat 2013;9:1591-4.

Bakhle YS. Structure of COX-1 and COX-2 enzymes and their interaction with inhibitors. Drugs Today (Barc). 1999;35:237-50.

Peskar BM. Role of cyclooxygenase isoforms in gastric mucosal defence. J Physiol Paris 2001;95:3-9.

Hawkey CJ. COX-1 and COX-2 inhibitors. Best Prac Res Clin Gastroenterol 2001;15:801-20.

Kalgutkar AS, Crews BC, Rowlinson SW. Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors. Proc Nat Acad Sci USA 2000;97:925-30.

Kaufmann WE, Worley PF, Pegg J. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc Nat Acad Sci USA 1996;93:2317-21.

Müller N, Myint AM, Schwarz MJ. The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders--relation to drug treatment. Dialogues Clin Neurosci 2009;11:319-32.

Muller N, Riedel M, Schwarz MJ. Psychotropic effects of COX-2 inhibitors--a possible new approach for the treatment of psychiatric disorders. Pharmacopsychiatry 2004;37:266-9.

Gałecki P, Talarowska M, Bobińska K. COX-2 gene expression is correlated with cognitive function in recurrent depressive disorder. Psychiatry Res 2014;215:488-90.

Guo JY, Li CY, Ruan YP. Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain. Eur J Pharmacol 2009;612:54-60.

Jaremka LM, Lindgren ME, Kiecolt-Glaser JK. Synergistic relationships among stress, depression, and troubled relationships: insights from psychoneuroimmunology. Depression Anxiety 2013;30:288-96.

Maciel IS, Silva RB, Morrone FB. Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice. PLoS One 2013;8:e77227. Doi:10.1371/journal.pone.0077227. [Article in Press]

Cichon S, Winge I, Mattheisen M. Brain-specific tryptophan hydroxylase 2 (TPH2): a functional Pro206Ser substitution and variation in the 5′-region are associated with bipolar affective disorder. Hum Mol Genet 2008;17:87-97.

Zill P, Baghai TC, Zwanzger P. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Mol Psychiatry 2004;9:1030-6.

Walther DJ, Bader MA. Unique central tryptophan hydroxylase isoform. Biochem Pharmacol 2003;66:1673-80.

McKinney J, Johansson S, Halmoy A. A loss-of-function mutation in tryptophan hydroxylase 2 segregating with attention-deficit/hyperactivity disorder. Mol Psychiatry 2008;13:365-7.

Shamir A, Shaltiel G, Levi I. Postmortem parietal cortex TPH2 expression is not altered in schizophrenic, unipolar-depressed, and bipolar patients vs control subjects. J Mol Neurosci 2005;26:33-7.

Brown SM, Peet E, Manuck SB. A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Mol Psychiatry 2005;10:884-8.

Zhou Z, Roy A, Lipsky R. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Arch Gen Psychiatry 2005;62:1109-18.

Breidenthal SE, White DJ, Glatt CE. Identification of genetic variants in the neuronal form of tryptophan hydroxylase (TPH2). Psychiatric Gen 2004;14:69-72.

Savelieva KV, Zhao S, Pogorelov VM. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS One 2008;3:e3301. Doi: 10.1371/journal. pone.0003301. [Article in Press]

Zhang Y, Zhang C, Yuan G. Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression. Behav Brain Funct 2010;6:49.

Lesch KP, Araragi N, Waider J. Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour. Philos Trans R Soc London Ser B 2012;367:2426-43.

Jacobsen JP, Siesser WB, Sachs BD. Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Mol Psychiatry 2012;17:694-704.

Zhou Z, Roy A, Lipsky R. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Arch Gen Psychiatry 2005;62:1109-18.

Cervo L, Canetta A, Calcagno E. Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression. J Neurosci 2005;25:8165-72.

Alenina N, Kikic D, Todiras M. Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc Natl Acad Sci U S A 2009;106:10332-7.

Lim JE, Pinsonneault J, Sadee W. Tryptophan hydroxylase 2 (TPH2) haplotypes predict levels of TPH2 mRNA expression in human pons. Mol Psychiatry 2007;12:491-501.

Walitza S, Renner TJ, Dempfle A. Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder. Mol Psychiatry 2005;10:1126-32.

Beaulieu JM. A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health. J Psychiatry Neurosci 2012;37:7-16.

Bijur GN, Jope RS. Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem 2003;87:1427-35.

Bijur GN, Jope RS. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3β. J Biol Chem 2001;276:37436-42.

Li X, Friedman AB, Roh MS. Anesthesia and post-mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase-3 in mouse brain. J Neurochem 2005;92:701-4.

Jope RS, Roh MS. Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets 2006;7:1421-34.

Belmaker RH, Agam G, Bersudsky Y. Role of GSK3β in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci U S A 2008;105:E23.

Kitagishi Y, Kobayashi M, Kikuta K. Roles of PI3K/AKT/GSK3/mTOR pathway in cell signaling of mental illnesses. Depression Research Treatment 2012;2012:752563. Doi:10.1155/2012/752563. [Article in Press]

Grimes CA, Jope RS. CREB DNA binding activity is inhibited by glycogen synthase kinase-3β and facilitated by lithium. J Neurochem 2001;78:1219-32.

Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 2004;113:1447-55.

Drago A, Monti B, De Ronchi D. Genetic variations within Metalloproteinases impact on the prophylaxis of depressive phases in bipolar patients. Neuropsychobiol 2014;69:76-82.

Stawarski M, Stefaniuk M, Wlodarczyk J. Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines. Front Neuroanat 2014;8:68.

Nazari M, Khodadadi H, Fathalizadeh J. Defective NF-kB transcription factor as the mediator of inflammatory responses: a study on depressed Iranian medical students. Clin Lab 2013;59:827-30.

Torres MA, Pace TW, Liu T. Predictors of depression in breast cancer patients treated with radiation: role of prior chemotherapy and nuclear factor kappa B. Cancer 2013;119:1951-9.

Koo JW, Russo SJ, Ferguson D. Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci U S A 2010;107:2669-74.

Lutgendorf SK, Lamkin DM, Jennings NB. Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma. Clin Cancer Res 2008;14:6839-46.

Hardingham GE. Pro-survival signalling from the NMDA receptor. Biochem Soc Trans 2006;34:936-38.

Hascup KN, Hascup ER, Stephens ML. Resting glutamate levels and rapid glutamate transients in the prefrontal cortex of the flinders sensitive line rat: a genetic rodent model of depression. Neuropsychopharmacol 2011;36:1769-77.

Valentine GW, Sanacora G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol 2009;78:431-9.

Lee Y, Son H, Kim G. Glutamine deficiency in the prefrontal cortex increases depressive-like behaviours in male mice. J Psychiatry Neurosci 2013;38:183-91.

Zou J, Wang YX, Dou FF. Glutamine synthetase downregulation reduces astrocyte protection against glutamate excitotoxicity to neurons. Neurochem Int 2010;56:577-84.

Renthal W, Nestler EJ. Chromatin regulation in drug addiction and depression. Dialogues Clin Neurosci 2009;11:257-68.

Covington HE, Vialou VF, LaPlant QC. Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci Lett 2011;493:122-6.

Jiang Y, Jakovcevski M, Bharadwaj R. SETDB1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B. J Neurosci 2010;30:7152-67.

Radley JJ, Kabbaj M, Jacobson L. Stress risk factors and stress-related pathology: neuroplasticity, epigenetics and endopheno-types. Stress (Amsterdam, Netherlands) 2011;14:481-97. Doi:10.3109/10253890.2011.604751. [Article in Press]

Covington HE, Maze I, LaPlant QC. Antidepressant actions of hdac inhibitors. J Neurosci 2009;29:11451-60.

Hunter RG, McCarthy KJ, Milne TA. Regulation of hippocampal H3 histone methylation by acute and chronic stress. Proc Natl Acad Sci U S A 2009;106:20912-7.

Hollis F, Duclot F, Gunjan A. Individual differences in the effect of social defeat on anhedonia and histone acetylation in the rat hippocampus. Hormone Behav 2011;59:331-7.

Sun H, Kennedy PJ, Nestler EJ. Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacol 2013;38:124-37.

Ferland CL, Schrader LA. Regulation of histone acetylation in the hippocampus of chronically stressed rats: a potential role of sirtuins. Neurosci 2011;174:104-14.

Benton CS, Miller BH, Skwerer S. Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains. Psychopharmacol 2012; 221:297-315.

Gundersen BB, Blendy JA. Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety. Neuropharmacol 2009;57:67-74




About this article

Title

ROLE OF ENZYMES IN THE PATHOGENESIS OF DEPRESSION

Date

04-04-2016

Additional Links

Manuscript Submission

Journal

Journal of Critical Reviews
Vol 3, Issue 2, 2016 Page: 11-16

Online ISSN

2394-5125

Statistics

943 Views | 138 Downloads

Authors & Affiliations

Vaibhav Walia
Division Pharmacology, Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, Haryana, India
India


Refbacks

  • There are currently no refbacks.