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01-09-2010 | Basic Neurosciences, Genetics and Immunology - Original Article

Chronic variable stress induces oxidative stress and decreases butyrylcholinesterase activity in blood of rats

Authors: Bárbara Tagliari, Tiago M. dos Santos, Aline A. Cunha, Daniela D. Lima, Débora Delwing, Angela Sitta, Carmem R. Vargas, Carla Dalmaz, Angela T. S. Wyse

Published in: Journal of Neural Transmission | Issue 9/2010

Abstract

Depressive disorders, including major depression, are serious and disabling, whose mechanisms are not clearly understood. Since life stressors contribute in some fashion to depression, chronic variable stress (CVS) has been used as an animal model of depression. In the present study we evaluated some parameters of oxidative stress [thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], and inflammatory markers (interleukin 6, C reactive protein, tumor necrosis factor-alpha and nitrites), as well as the activity of butyrylcholinesterase in blood of rats subjected to chronic stress. Homocysteine and folate levels also were measured. Stressed animals were submitted to different mild stressors for 40 days. After CVS, a reduction in weight gain was observed in the stressed group, as well as an increase in immobility time in the forced swimming test as compared with controls. Stressed animals presented a significant increase on TBARS and SOD/CAT ratio, but stress did not alter GPx activity and any inflammatory parameters studied. CVS caused a significant inhibition on serum butyrylcholinesterase activity. Stressed rats had higher plasmatic levels of homocysteine without differences in folate levels. Although it is difficult to extrapolate our findings to the human condition, the alterations observed in this work may be useful to help to understand, at least in part, the pathophysiology of depressive disorders.

Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefPubMed

Alcantara VM, Chautard-Freire-Maia EA, Scartezini M, Cerci MS, Braun-Prado K, Picheth G (2002) Butyrylcholinesterase activity and risk factors for coronary artery disease. Scan J Clin Lab Invest 62:399–404CrossRef

Alexopoulos P, Topalidis S, Irmisch G, Prehn K, Jung SU, Poppe K, Sebb H, Perneczky R, Kurz A, Bleich S, Herpertz SC (2010) Homocysteine and cognitive function in geriatric depression. Neuropsychobiology 61(2):97–104CrossRefPubMed

Bao AM, Meynena G, Swaab DF (2008) The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev 57:531–553CrossRefPubMed

Belmaker RH, Agam G (2008) Major depressive disorder. N Engl J Med 358(1):55–68CrossRefPubMed

Bilici M, Efe H, Köroğlu MA, Uydu HA, Bekaroğlu M, Değer O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64(1):43–51CrossRefPubMed

Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH (2000) Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 69:228–232CrossRefPubMed

Bradford MM (1976) A rapid and sensitive method for the quantification of micrograms quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMed

Cascalheira JF, Parreira MC, Viegas AN, Faria MC, Domingues FC (2008) Serum homocysteine: relationship with circulating levels of cortisol and ascorbate. Ann Nutr Metab 53(1):67–74CrossRefPubMed

Charney DS, Manji HK (2004) Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for intervention. Sci. STKE 225:1–11

Cumurcu BE, Ozyurt H, Etikan I, Demir S, Karlidag R (2009) Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment. Psychiatry Clin Neurosci 63(5):639–645CrossRefPubMed

Dantzer R (2006) Cytokine, sickness behavior and depression. Neurol Clin 24(3):441–446CrossRefPubMed

Darvesh S, Hopkins DA, Geula C (2003) Neurobiology of butyrylcholinesterase. Nat Rev Neurosci 17:131–138CrossRef

de Souza FG, Rodrigues MD, Tufik S, Nobrega JN, D’Almeida V (2006) Acute stressor-selective effects on homocysteine metabolism and oxidative stress parameters in female rats. Pharmacol Biochem Behav 85(2):400–407CrossRefPubMed

Del Rio D, Stewart AJ, Pellegrini N (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15:316–328CrossRefPubMed

Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431CrossRefPubMed

Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95CrossRefPubMed

Faraci FM, Lentz SR (2004) Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke 35:345–347CrossRefPubMed

Ferreira AG, Lima DD, Delwing D, Mackedanz V, Tagliari B, Kolling J, Schuck PF, Wajner M, Wyse AT (2010) Proline impairs energy metabolism in cerebral cortex of young rats. Metab Brain Dis 25(2):161–168CrossRefPubMed

Folstein M, Liu T, Peter I, Buel J, Arsenault L, Scott T, Qiu WW (2007) Homocysteine hypothesis of depression. Am J Psychiatry 16:861–867CrossRef

Gamaro GD, Manoli LP, Torres ILS, Silveira R, Dalmaz C (2003) Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structures. Neurochem Int 42:107–114CrossRefPubMed

Gamaro GD, Prediger ME, Bassani MG, Dalmaz C (2008) Fluoxetine alters feeding behavior and leptin levels in chronically-stressed rats. Pharmacol Biochem Behav 90:312–317CrossRefPubMed

Gillespie CF, Nemeroff CB (2005) Hypercortisolemia and depression. Psychosom Med 67:26–28CrossRef

Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, Yirmiya R (2008) Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13(7):717–728CrossRefPubMed

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and [15N]nitrate in biological fluids. Anal Biochem 126:131–138CrossRefPubMed

Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kühn M, Schuld A, Pollmächer T (1999) Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res 33:407–418CrossRefPubMed

Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658CrossRefPubMed

Halliwell B, Gutteridge JMC (2006) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford

Harro J, Tõnissaar M, Eller M, Kask A, Oreland L (2001) Chronic variable stress and partial 5-HT denervation by parachloroamphetamine treatment in the rat: effects on behavior and monoamine neurochemistry. Brain Res 899(1–2):227–239CrossRefPubMed

Jendricko T, Vidović A, Grubisić-Ilić M, Romić Z, Kovacić Z, Kozarić-Kovacić D (2009) Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 33(1):134–140CrossRefPubMed

Johnson AK, Grippo AJ (2006) Sadness and broken hearts: neurohumoral mechanisms and co-morbidity of ischemic heart disease and psychological depression. J Physiol Pharmacol 57(S11):5–29PubMed

Katz RJ, Hersh S (1981) Amitriptyline and scopolamine in an animal model of depression. Neurosci Biobehav Rev 5:265–271CrossRefPubMed

Kelly CB, McDonnell AP, Johnston TG, Mulholland C, Cooper SJ, McMaster D, Evans A, Whitehead AS (2004) The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J. Psychopharmacol 18(4):567–571CrossRefPubMed

Kelner MJ, Bagnell R, Montoya M, Estes L, Uglik SF, Cerutti P (1995) Transfection with human copper-zinc superoxide dismutase induces bidirectional alterations in other antioxidant enzymes, proteins, growth factor response, and paraquat resistance. Free Radic Biol Med 18:497–506CrossRefPubMed

Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R (2003) Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep 8(6):365–370CrossRefPubMed

Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Yoon JS (2008) Predictive value of folate, vitamin B12 and homocysteine levels in latelife depression. Br J Psychiatry 192:268–274CrossRefPubMed

Konarska M, Stewart RE, McCarty R (1990) Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rats. Behav Neural Biol 53:231–243CrossRefPubMed

Kubera M, Symbirtsev A, Basta-Kaim A, Borycz J, Roman A, Papp M, Claesson M (1996) Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. Pol J Pharmacol 48(5):503–506PubMed

Kunz M, Gama CS, Andreazza AC, Salvador M, Ceresér KM, Gomes FA, Belmonte-de-Abreu PS, Berk M, Kapczinski F (2008) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 32(7):1677–1681CrossRefPubMed

Levine J, Timinsky I, Vishne T, Dwolatzky T, Roitman S, Kaplan Z, Kotler M, Sela BA, Spivak B (2008) Elevated serum homocysteine levels in male patients with PTSD. Depress Anxiety 25(11):E154–E157CrossRefPubMed

Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, Arnelle DR, Stamler JS (1997) Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 94:5923–5928CrossRefPubMed

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–267PubMed

Lucca G, Comim CM, Valvassori SS, Réus GZ, Vuolo F, Petronilho F, Dal-Pizzol F, Gavioli EC, Quevedo J (2009) Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 54:358–362CrossRefPubMed

Lucinio J, Wong ML (1999) The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry 4:317–327CrossRef

Madrigal JLM, Olivenza R, Moro MA, Lisasoain I, Lorenzo P, Rodrigo J, Leza JC (2001) Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 24(4):420–429CrossRefPubMed

Maes M, Yirmya R, Noraberg J, Brene S, Hibbeln J, Perinii G, Kubera M, Bob P, Lerer B, Maj M (2009) The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 24:27–53CrossRefPubMed

Magera MJ, Lacey JM, Casetta B, Rinaldo P (1999) Method for the determination of total homocysteine in plasma and urine by stable isotope dilution and electrospray tandem mass spectrometry. Clin Chem 45:1517–1522PubMed

Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russel J (2007) Neurobiology of depression: an integrated view of key findings. Int J Clin Pract 61(12):2030–2040CrossRef

Manji HK, Drevets WC, Charney DS (2001) The cellular neurobiology of depression. Nat Med 7(5):541–547CrossRefPubMed

Marin MT, Cruz FC, Planeta CS (2007) Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats. Physiol Behav 90(1):29–35CrossRefPubMed

Marklund S (1985) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 243–247

Massoulié J, Pezzementi L, Bon S, Krejci E, Vallette FM (1993) Molecular and cellular biology of cholinesterases. Prog Neurobiol 41(1):31–91CrossRefPubMed

Matés JM, Pérez-Gomes C, De Castro IN (1999) Antioxidant enzymes and human diseases. Clin Biochem 32(8):595–603CrossRefPubMed

Matté C, Durigon E, Stefanello FM, Cipriani F, Wajner M, Wyse ATS (2006) Folic acid pretreatment prevents the reduction of Na(+),K(+)-ATPase and butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia. Int J Dev Neurosci 24(1):3–8CrossRefPubMed

Matté C, Mackedanz V, Stefanello FM, Scherer EB, Andreazza AC, Zanotto C, Moro AM, Garcia SC, Gonçalves CA, Erdtmann B, Salvador M, Wyse ATS (2009) Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int 54(1):7–13CrossRefPubMed

Mattson MP, Shea TB (2003) Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26:137–146CrossRefPubMed

Mesulam MM, Guillozet A, Shaw P, Levey A, Duysen EG, Lockridge O (2002) Acethylcolynesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyse acetylcholine. Neuroscience 110:627–639CrossRefPubMed

Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741CrossRefPubMed

Mormède C, Castanon N, Médina C, Moze E, Lestage J, Leveu PJ, Dantzer R (2003) Chronic mild stress in mice decreases peripheral cytokine and increases central cytokine expression independently of IL-10 regulation of the cytokine network. Neuroimmunomodulation 10:359–366

Ng F, Berk M, Dean O, Bush AI (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 21:1–26

Ni Y, Su M, Lin J, Wang X, Qiu Y, Zhao A, Chen T, Jia W (2008) Metabolic profiling reveals disorder of amino acid metabolism in four brain regions from a rat model of chronic unpredictable mild stress. FEBS Lett 582(17):2627–2636CrossRefPubMed

Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefPubMed

Olivenza R, Moro MA, Lisasoain I, Lorenzo P, Fernandez AP, Rodrigo J, Boscá L, Leza JC (2000) Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem 74:785–791CrossRefPubMed

Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336PubMed

Rada P, Colasante C, Skirzewski M, Hernandez L, Hoebel B (2006) Behavioral depression in the swim test causes a biphasic, long-lasting change in accumbens acetylcholine release, with partial compensation by acetylcholinesterase and muscarinic-1 receptors. Neuroscience 141:67–76CrossRefPubMed

Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygård O, Vollset SE (2006) The Hordaland homocysteine study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr 136(6):1731S–1740SPubMed

Reif A, Schneider MF, Kamolz S, Pfuhlmann B (2003) Homocysteinemia in psychiatric disorders: association with dementia and depression, but not schizophrenia in female patients. J Neural Transm 110:1401–1411CrossRefPubMed

Resler G, Lavie R, Campos J, Mata S, Urbina M, García A, Apitz R, Lima L (2008) Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes. Neuroimmunomodulation 15(3):145–152CrossRefPubMed

Röhrdanz E, Obertrifter B, Ohler S, Tran-Thi Q, Kahl R (2000) Influence of Adriamycin and paraquat on antioxidant enzyme expression in primary rat hepatocytes. Arch Toxicol 74:231–237CrossRefPubMed

Sapolsky RM (1996) Why stress is bad for your brain. Science 273:749–750CrossRefPubMed

Schallreuter KU, Elwary S (2007) Hydrogen peroxide regulates the cholinergic signal in a concentration dependent manner. Life Sci 80(24–25):2221–2226CrossRefPubMed

Scherer EB, Stefanello FM, Mattos C, Netto CA, Wyse ATS (2007) Homocysteine reduces cholinesterase activity in rat and human serum. Int J Dev Neurosci 25(4):201–205CrossRefPubMed

Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 29(2):201–217CrossRefPubMed

Stefanello FM, Franzon R, Tagliari B, Wannmacher C, Wajner M, Wyse ATS (2005) Reduction of butyrylcholinesterase activity in rat serum subjected to hyperhomocysteinemia. Metab Brain Dis 20(2):97–103CrossRefPubMed

Steptoe A, Kunz-Ebrecht SR, Owen N (2003) Lack of association between depressive symptoms and markers of immune and vascular inflammation in middle-aged men and women. Psychol Med 33:667–674CrossRefPubMed

Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4:141–194CrossRefPubMed

Tagliari B, Noschang CG, Ferreira AGK, Ferrari OA, Feksa LR, Wannmacher CMD, Dalmaz C, Wyse ATS (2010) Chronic variable stress impairs energy metabolism in brain of rats. Metab Brain Dis 25(2):169–176CrossRefPubMed

Tolmunen T, Hintikka J, Voutilainen S, Ruusunen A, Alfthan G, Nyyssönen K, Viinamäki H, Kaplan GA, Salonen JT (2004) Association between depressive symptoms and serum concentrations of homocysteine in men: a population study. Am J Clin Nutr 80:1574–1578PubMed

Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859CrossRefPubMed

Triantafyllou N, Evangelopoulos ME, Kimiskidis VK, Kararizou E, Boufidou F, Fountoulakis KN, Siamouli M, Konstantinos N, Nikolaou C, Sfagos C, Vlaikidis N, Vassilopoulos D (2008) Increased plasma homocysteine levels in patients with multiple sclerosis and depression. Ann Gen Psychiatry 7:17–21CrossRefPubMed

Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–332CrossRefPubMed

Wilhelm J, Muller E, de Zwaan M, Fischer J, Hillemacher T, Komhuber J, Bleich S, Frieling H (2010) Elevation of homocysteine levels is only partially reversed after therapy in females with eating disorders. J Neural Transm 117:521–527CrossRefPubMed

Wilner P (2005) Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52:90–110CrossRef

Wilson DO, Johnson P (2000) Exercise modulates antioxidant enzyme gene expression in rat myocardium and liver. J Appl Physiol 88:1791–1796PubMed

Wyse ATS, Zugno AI, Streck EL, Matté C, Calcagnotto T, Wannmacher CM, Wajner M (2002) Inhibition of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to acute administration of homocysteine is prevented by vitamins E and C treatment. Neurochem Res 27(12):1685–1689CrossRefPubMed

You JM, Yun SJ, Nam KN, Kang C, Won R, Lee EH (2009) Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharmacol 87(6):440–447CrossRefPubMed

Zafir A, Banu N (2009) Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress 12(2):167–177CrossRefPubMed

Title: Chronic variable stress induces oxidative stress and decreases butyrylcholinesterase activity in blood of rats
Authors: Bárbara Tagliari
Tiago M. dos Santos
Aline A. Cunha
Daniela D. Lima
Débora Delwing
Angela Sitta
Carmem R. Vargas
Carla Dalmaz
Angela T. S. Wyse
Publication date: 01-09-2010
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 9/2010
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-010-0445-0

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Chronic variable stress induces oxidative stress and decreases butyrylcholinesterase activity in blood of rats

Abstract

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