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Brain energy metabolism is increased by chronic administration of bupropion

  • Gabriela K. Ferreira (a1) (a2), Gislaine T. Rezin (a1) (a2), Mariane R. Cardoso (a1) (a2), Cinara L. Gonçalves (a1) (a2), Lislaine S. Borges (a1) (a2), Júlia S. Vieira (a1) (a2), Lara M. Gomes (a1) (a2), Alexandra I. Zugno (a2) (a3), João Quevedo (a2) (a3) and Emilio L. Streck (a1) (a2)...

Extract

Objectives: Based on the hypothesis that energy impairment may be involved in the pathophysiology of depression, we evaluated the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase (SDH), mitochondrial respiratory chain complexes I, II, II-III, IV and creatine kinase (CK) in the brain of rats submitted to chronic administration of bupropion.

Methods: Animals received daily administration of bupropion dissolved in saline (10 mg/kg, intraperitoneal) at 1.0 ml/kg body weight. The rats received injections once a day for 14 days; control rats received an equivalent volume of saline. Twelve hours after the last administration, the rats were killed by decapitation and brain was rapidly removed and kept on an ice plate. The activities of the enzymes were measured in different brain areas.

Results: We observed that the activities of citrate synthase and malate dehydrogenase, mithocondrial respiratory chain complexes I, II-III and IV and CK were not altered after chronic administration of bupropion. However, SDH activity was increased in the prefrontal cortex and cerebellum. In the hippocampus, cerebellum and striatum the activity of complex II was increased after chronic administration of bupropion.

Conclusions: Our results demonstrated that bupropion increased some enzymes of brain energy metabolism. These findings are in accordance with other studies which showed that some antidepressants may improve energy metabolism. The present results reinforce the hypothesis that antidepressants modulate brain energy metabolism.

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Corresponding author

Prof. Emilio L. Streck, PharmD, PhD, Laboratório de Bioenergética, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil. Tel: +55 48 3431 2539; Fax: +55 48 3431 2750; E-mail: emiliostreck@gmail.com

References

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1.Rex, A, Schickert, R, Fink, H.Antidepressant-like effect of nicotinamide adenine dinucleotide in the forced swim test rats. Pharmacol Biochem Behav 2004;77:303307.
2.Murray, CJL. The global burden of disease. In: Murray, CJ, Lopez, AD, eds. Global burden of disease and injury series. Boston, MA: The Harvard School of Public Health, 1996.
3.Shelton, RC.The molecular neurobiology of depression. Psychiatric Clin North Am 2007;30:111.
4.Kessler, RC, Gonagle, KA, Zhao, S et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:819.
5.Kessler, RC, Rubinow, DR, Holmes, C, Abelson, JM, Zhao, S.The epidemiology of DSM-III-R bipolar disorder in a general population survey. Psychol Med 1997;27: 10791089.
6.Longone, P, Rupprecht, R, Manieri, GA, Bernardi, G, Romeo, E, Pasini, A.The complex roles of neurosteroids in depression and anxiety disorders. Neurochem Int 2008;52: 596601.
7.Mico, JA, Ardid, D, Berrocoso, E, Eschalier, A.Antidepressants and pain. Trends Pharmacol Sci 2006;7:348354.
8.Stahl, SM, Pradko, JF, Haight, BR, Modell, JB, Rockett, CB, Learned-Coughlin, S.A review of the neuropharmacology of bupropion, a dual norepinephrin and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry 2004;6:159166.
9.Duman, RS, Nakagawa, S, Malberg, J.Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology 2001;25:836844.
10.Jacobs, BL, Praag, H, Gage, FH.Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 2000;5:262269.
11.Heales, SJ, Bolaños, JP, Stewart, VC, Brookes, PS, Land, JM, Clark, JB.Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1999;1410:215228.
12.Blass, JP.Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 2001;66:851856.
13.Schurr, A.Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 2002;41:18.
14.Madrigal, JL, Olivenza, R, Moro, MA et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 2001;24:420429.
15.Boekema, EJ, Braun, HP.Supramolecular structure of the mitochondrial oxidative phosphorylation system. J Chem Biol 2007;282:14.
16.Kelly, D, Gordon, J, Alpers, R et al. The tissue-specific expression and developmental regulation of two nuclear genes encoding rat mitochondrial proteins. Medium chain acyl-CoA dehydrogenase and mitochondrial malate dehydrogenase. J Biol Chem 1989;264:1892118925.
17.Corrêa, C, Amboni, G, Assis, LC et al. Effects of lithium and valproate on hippocampus citrate synthase activity in an animal model of mania. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:887891.
18.Tyler, D.The mitochondrion in health and diseases. New York: VCH Publishers, 1992.
19.Brennan, WA, Bird, ED, Aprille, JR.Regional mitochondrial respiratory activity in Huntington's disease brain. J Neurochem 1985;44:1948.
20.Heales, SJ, Bolanõs, JP, Stewart, VC, Brookes, PS, Land, JM, Clark, JB.Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1999;1410:215228.
21.Schurr, A.Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 2002;41:18.
22.Monsalve, M, Borniquel, S, Valle, I, Lamas, S.Mitochondrial dysfunction in human pathologies. Front Biosci 2007;12:11311153.
23.Moreira, PI, Santos, MS, Oliveira, CR.Alzheimer's disease: a lesson from mitochondrial dysfunction. Antioxid Redox Signal 2007;9:16211630.
24.Moreira, PI, Santos, MS, Seiça, R, Oliveira, CR.Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes. J Neurol Sci 2007;257:206214.
25.Bessman, SP, Carpenter, CL.The Creatine-Creatine phosphate energy shuttle. Annu Rev Biochem 1985;54:831865.
26.Wallimann, T, Wyss, M, Brdiczka, D, Nicolay, K, Eppenberger, HM.Intracellular compartmentation, structure and function of Creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphoCreatine circuit' for cellular energy homeostasis. Biochem J 1992;281: 2140.
27.Streck, EL, Amboni, G, Scaini, G et al. Brain creatine kinase activity in an animal model of mania. Life Sci 2008; 82:424429.
28.Burigo, M, Roza, CA, Bassani, C et al. Decreased Creatine kinase activity caused by electroconvulsive shock. Neurochem Res 2006;31:877881.
29.Kanarick, M, Matrov, D, Kõiv, K, Eller, M, Tõnissaar, M, Harro, J.Changes in regional long-term oxidative metabolism induced by partial serotonergic denervation and chronic variable stress in rat brain. Neurochem Int 2008;52: 432437.
30.Stanyer, L, Jorgensen, W, Hori, O, Clark, JB, Heales, SJ.Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction. Neurochem Int 2008;53:95101.
31.Kitamira, Y, Fujitani, Y, Kitagawa, K et al. Effects of imipramine and bupropion on the duration of immobility of acth-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA. Biol Pharm Bull 2008;31:246249.
32.Lowry, OH, Rosebough, NG, Farr, AL et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265275.
33.Shepherd, D, Garland, PB.The kinetic properties of citrate synthase from rat liver mitochondria. Biochem J 1969;114:597610.
34.Kitto, GB.Intra- and extramitochondrial malate dehydrogenases from chicken and tuna heart. Meth Enzymol 1969;XIII:106116.
35.Fischer, JC, Ruitenbeek, W, Berden, JA et al. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 1985;153:2326.
36.Cassina, A, Radi, R.Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996;328:309316.
37.Rustin, P, Chretien, D, Bourgeron, T et al. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:3551.
38.Hughes, BP.A method for estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathologic sera. Clin Chim Acta 1962;7:597604.
39.Arnaiz, SL, Coronel, MF, Boveris, A.Nitric oxide, superoxide and hydrogen peroxide production in brain mitochondria after haloperidol treatment. Nitric Oxide 1999;3: 235243.
40.Adam-Vizi, V.Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 2005;7:11401149.
41.Assis, LC, Rezin, GT, Comim, CM et al. Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats. Rev Bras Psiquiatr 2009; 31:247252.
42.Scaini, G, Santos, PM, Benedet, J et al. Evaluation of krebs cycle enzymes in the brain of rats after chronic administration of antidepressants. Brain Res Bull 2010;52: 224227.
43.Gardner, A, Johansson, A, Wibom, R et al. Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J Affect Dis 2003;76:5568.
44.Madrigal, JL, Olivenza, R, Moro, MA et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 2001;24:420429.
45.Rezin, GT, Cardoso, MR, Gonçalves, CL et al. Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int 2008;53:395400.
46.Wellman, PJ.Modulation of eating by central catecholamine systems. Curr Drug Targets 2005;6:191199.
47.Ascher, JA, Cole, JO, Colin, JN et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 1995;56:395401.
48.Stahl, SM, Pradko, JF, Haight, BR, Modell, JG, Rockett, CB, Learned-Coughlin, S.A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry 2004;6:159166.
49.Scaini, G, Maggi, DD, De-Nês, BT et al. Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants. Acta Neuropsychiatrica 2011; 23:112118.
50.Santos, PM, Scaini, G, Rezin, GT et al. Brain creatine kinase activity is increased by chronic administration of paroxetine. Brain Res Bull 2009;80:327330.
51.Agostinho, FR, Scaini, G, Ferreira, GK et al. Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase activity in rat brain. Brain Res Bull 2009;80: 337340.

Keywords

Brain energy metabolism is increased by chronic administration of bupropion

  • Gabriela K. Ferreira (a1) (a2), Gislaine T. Rezin (a1) (a2), Mariane R. Cardoso (a1) (a2), Cinara L. Gonçalves (a1) (a2), Lislaine S. Borges (a1) (a2), Júlia S. Vieira (a1) (a2), Lara M. Gomes (a1) (a2), Alexandra I. Zugno (a2) (a3), João Quevedo (a2) (a3) and Emilio L. Streck (a1) (a2)...

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