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Differential effects of escitalopram administration on metabolic parameters of cortical and subcortical brain regions of Wistar rats

Published online by Cambridge University Press:  24 June 2014

Cinara L. Gonçalves ,
Gislaine T. Rezin ,
Gabriela K. Ferreira ,
Isabela C. Jeremias ,
Mariane R. Cardoso ,
Milena Carvalho-Silva ,
Alexandra I. Zugno ,
João Quevedo  and
Emilio L. Streck
Cinara L. Gonçalves
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Gislaine T. Rezin
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Gabriela K. Ferreira
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Isabela C. Jeremias
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Mariane R. Cardoso
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Milena Carvalho-Silva
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Alexandra I. Zugno
Affiliation:
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
João Quevedo
Affiliation:
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
Emilio L. Streck*
Affiliation:
Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil
*
Emilio L. Streck, Laboratório de Bioenergética, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. Tel: +554834312539; E-mail: emiliostreck@gmail.com
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Extract

Objective: Considering that mitochondria may be drug targets and some characteristics of drug–mitochondria interactions may still be misjudged because of the difficulty in foreseeing and understanding all possible implications of the complex pathophysiology of mitochondria, our study aimed to investigate the effect of escitalopram on the activity of enzymes of mitochondrial energy metabolism.

Methods: Animals received daily administration of escitalopram dissolved in saline [10 mg/kg, intraperitoneal (IP)] at 1.0 ml/kg volume for 14 days. Control rats received an equivalent volume of saline, 1.0 ml/kg (IP), for the same treatment period. Twelve hours after last injection, rats were killed by decapitation and brain areas were rapidly isolated. The samples were homogenised and the activities of mitochondrial respiratory chain complexes, some enzymes of Krebs cycle (citrate synthase, malate dehydrogenase and succinate dehydrogenase) and creatine kinase were measured.

Results: We verified that chronic administration of escitalopram decreased the activities of complexes I and II–III in cerebellum, hippocampus, striatum and posterior cortex whereas prefrontal cortex was not affected. Complex II activity was decreased only in striatum without affecting prefrontal cortex, hippocampus, cerebellum and posterior cortex. However, chronic administration of escitalopram did not affect complex IV and enzymes of Krebs cycle activities as well as creatine kinase.

Conclusion: In this study we showed a decrease in the activities of complexes I and II–III in most of the brain structures analysed and complex II activity was decreased only in striatum. However, it remains to be determined if mitochondrial dysfunction is rather a causal or a consequential event of abnormal signalling.

Keywords

braincreatine kinaseescitalopramKrebs cyclemitochondrial respiratory chain
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 3 , June 2012 , pp. 147 - 154
Copyright
Copyright © Cambridge University Press 2011

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References

1.Kessler, RC, Walters, EE.Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey. Depress Anxiety 1998;7:3–14.3.0.CO;2-F>CrossRefGoogle Scholar
2.Turner, JR, Gil, AG.Psychiatric and substance use disorders in South Florida racial/ethnic and gender contrasts in a young adult cohort. Arch Gen Psychiatry 2002;59:43–50.CrossRefGoogle Scholar
3.Kessler, RC, Berglund, P, Demler, O, Jin, R, Kr, Merikans, Walters, EE.Lifetime prevalence and age-of-onset distributions of DSM-IV disorder in the national comorbidity survey replication. Arch Gen Psychiatry 2005;62:593–768.CrossRefGoogle ScholarPubMed
4.Rex, A, Schickert, R, Fink, H.Antidepressant-like effect of nicotinamide adenine dinucleotide in the forced swim test in rats. Pharmacol Biochem Behav 2004;77:303–307.CrossRefGoogle ScholarPubMed
5.Kiss, JP.Theory of active antidepressants: a nonsynaptic approach to the treatment of depression, Neurochem Int 2008;52:34–39.CrossRefGoogle Scholar
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;52:596–601.CrossRefGoogle ScholarPubMed
7.Greenberg, PE, Stiglin, LE, Finkelstein, SN, Berndt, ER, 1993. The economic burden of depression in 1990. J Clin Psychiatry 1990;54:405–418.Google ScholarPubMed
8.World Health Organization: Programmes and projects/mental health/disorders management/depression. Retrieved March 1, 2010, from URL http://www.who.int/mental_health/management/depression/definition/en/Google Scholar
9.Cannon, TD, Keller, MC.Endophenotypes in the genetic analyses of mental disorders. Annu Rev Clin Psychol 2006;2:267–290.CrossRefGoogle ScholarPubMed
10.Skolnick, P.Beyond monoamine-based therapies: clues to new approaches. J Clin Psychiatry 2002;63:19–23.Google ScholarPubMed
11.Charney, DS.Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 1998;59:11–14.Google ScholarPubMed
12.Brunello, N, Mendlewicz, J, Kasper, S et al. The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. Eur Neuropsychopharmacology 2002;12:461–475.CrossRefGoogle ScholarPubMed
13.Johnson, AM.Paroxetine: a pharmacological review. Int Clin Psychopharmacol 1992;6:15–24.CrossRefGoogle ScholarPubMed
14.Richelson, E.Pharmacology of anti-depressants – characteristics of the ideal drug. Mayo Clin Proc 1999;69: 1069–1081.CrossRefGoogle Scholar
15.David, DJ, Bourin, M, Jego, G, Przybylski, C, Jolliet, P, Gardier, AM.Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice. Br J Pharmacol 2003;140:1128–1136.CrossRefGoogle ScholarPubMed
16.Borsini, F, Podhorna, J, Marazziti, D.Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology 2002;163:121–141.CrossRefGoogle ScholarPubMed
17.Brennan, WA, Bird, ED, Aprille, JR.Regional mitochondrial respiratory activity in Huntington's disease brain. J Neurochem 1985;44:1948.CrossRefGoogle ScholarPubMed
18.Heales, SJ, Bolanõs, JP, Stewart, VC, Brookes, PS, Land, JM, Clark, JB.Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1999;1410: 215–228.CrossRefGoogle ScholarPubMed
19.Blass, JP.Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 2001;66:851–856.CrossRefGoogle ScholarPubMed
20.Schurr, A.Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 2002;41:1–8.CrossRefGoogle ScholarPubMed
21.Monsalve, M, Borniquel, S, Valle, I, Lamas, S.Mitochondrial dysfunction in human pathologies. Front Biosci 2007;12:1131–1153.CrossRefGoogle ScholarPubMed
22.Moreira, PI, Santos, MS, Oliveira, CR.Alzheimer's disease: a lesson from mitochondrial dysfunction. Antioxid Redox Signal 2007;9:1621–1630.CrossRefGoogle ScholarPubMed
23.Moreira, PI, Santos, MS, Seiça, R, Oliveira, CR.Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes. J Neurol Sci 2007;257:206–214.CrossRefGoogle Scholar
24.Calabrese, V, Scapagnini, G, Giuffrida-Stella, AM, Bates, TE, Clark, JB.Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 2001;26:739–764.CrossRefGoogle ScholarPubMed
25.Boekema, EJ, Braun, HP.Supramolecular structure of the mitochondrial oxidative phosphorylation system. J Biol Chem 2007;282:1–4.CrossRefGoogle ScholarPubMed
26.Kelly, D, Gordon, J, Alpers, R, Strauss, AW.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;264:18921–18925.CrossRefGoogle ScholarPubMed
27.Shepherd, D, Garland, PB.The kinetic properties of citrate synthase from rat liver mitochondria. Biochem J 1969;114:597–610.CrossRefGoogle ScholarPubMed
28.Labrou, NE, Clonis, YD.L-Malate dehydrogenase from Pseudomonas stutzeri: purification and characterization. Arch Biochem Biophys 1997;337:103–114.CrossRefGoogle ScholarPubMed
29.Tyler, D.The mitochondrion in health and diseases. New York: VCH Publishers, 1992.Google Scholar
30.Rustin, P, Munnich, A, Rötig, A.Succinate dehydrogenase and human diseases: newinsights into a well-known enzyme. Eur J Hum Genet 2002;10:289–291.CrossRefGoogle Scholar
31.Tomimoto, H, Yamamoto, K, Homburger, HA, Yanagihara, T.Immunoelectron microscopic investigation of creatine kinase BB-isoenzyme after cerebral ischemia in gerbils, Acta Neuropathol 1993;86:447–455.CrossRefGoogle ScholarPubMed
32.Hamman, BL, Bittl, JA, Jacobus, WE et al. Inhibition of the creatine kinase reaction decreases the contractile reserve of isolated rat hearts. Am J Physiol 1995;269:1030–1036.Google ScholarPubMed
33.Gross, WL, Bak, MI, Ingwall, JS et al. Nitric oxide inhibits creatine kinase and regulates heart contractile reserve. Proc Natl Acad Sci U S A 1996;93:5604–5609.CrossRefGoogle ScholarPubMed
34.David, S, Shoemaker, M, Haley, BE.Abnormal properties of creatine kinase in Alzheimer's disease brain: correlation of reduced enzyme activity and active site photolabeling with aberrant cytosol-membrane partitioning. Brain Res Mol Brain Res 1998;54:276–287.CrossRefGoogle ScholarPubMed
35.Aksenov, M, Aksenova, M, Butterfield, DA, Markesbery, WR.Oxidative modification of creatine kinase BB in Alzheimer's disease brain. J Neurochem 2000;74: 2520–2527.CrossRefGoogle ScholarPubMed
36.Jayatissa, MN, Bisgaard, C, Tingström, A, Papp, M, Wiborg, O.Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology 2006;31: 2395–2404.CrossRefGoogle Scholar
37.Lowry, OH, Rosebough, NG, Farr, AL, Randall, RJ.Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.CrossRefGoogle ScholarPubMed
38.Cassina, A, Radi, R.Differential inhibitory Aation of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996;328:309–316.CrossRefGoogle ScholarPubMed
39.Fischer, JC, Ruitenbeek, W, Berden, JA, Trijbels, JM.Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 1985;153:23–26.CrossRefGoogle ScholarPubMed
40.Rustin, P, Chretien, D, Bourgeron, T et al. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:35–51.CrossRefGoogle ScholarPubMed
41.Kitto, GB.Intra- and extramitochondrial malate dehydrogenases from chicken and tuna heart. Methods Enzymol 1969;8:106–116.CrossRefGoogle Scholar
42.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;7:597–604.CrossRefGoogle Scholar
43.Mattson, MP, Gleichmann, M, Cheng, A.Mitochondria in neuroplasticity and neurological disorders. Neuron 2008;60:748–766.CrossRefGoogle ScholarPubMed
44.Retter, L, Mayer-Takacs, D, Adam-Vizi, V.The effect of bovine serum albumin on the membrane potential and reactive oxygen species generation in succinate-supported isolated brain mitochondria. Neurochem Int 2007;50:139–147.CrossRefGoogle Scholar
45.Petrosillo, G, Matera, M, Casanova, G, Ruggiero, FM, Paradies, G.Mitochondrial dysfunction in rat brain with aging: involvement of complex I, reactive oxygen species and cardiolipin. Neurochem Int 2008;53:126–131.CrossRefGoogle ScholarPubMed
46.Kanarik, 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;52:432–437.CrossRefGoogle ScholarPubMed
47.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;53:95–101.CrossRefGoogle ScholarPubMed
48.Madrigal, JL, Olivenza, R, Moro, M et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 2001;24:420–429.CrossRefGoogle ScholarPubMed
49.Barrett, SL, Kelly, C, Bell, R, King, DJ.Gender influences the detection of spatial working memory deficits in bipolar disorder. Bipolar Disord 2008;10:647–654.CrossRefGoogle ScholarPubMed
50.Quraishi, S, Walshe, M, Mcdonald, C et al. Memory functioning in familial bipolar I disorder patients and their relatives. Bipolar Disord 2009;11:209–214.CrossRefGoogle ScholarPubMed
51.Streck, EL, Amboni, G, Scaini, G et al. Brain Creatine kinase activity in an animal model of mania. Life Sci 2008;82:424–429.CrossRefGoogle Scholar
52.Burigo, M, Roza, CA, Bassani, C et al. Decreased Creatine kinase activity caused by electroconvulsive shock. Neurochem Res 2006;31:877–881.CrossRefGoogle ScholarPubMed
53.Gamaro, GD, Streck, EL, Matté, C, Prediger, ME, Wyse, AT, Dalmaz, C.Reduction of hippocampal Na+, K+-ATPase activity in rats subjected to an experimental model of depression. Neurochem Res 2003;28:1339–1344.CrossRefGoogle Scholar
54.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;53:395–400.CrossRefGoogle Scholar
55.Ferretti, V, Roullet, P, Sargolini, F et al. Ventral striatal plasticity and spatial memory. Proc Natl Acad Sci U S A 2010;107:7945–7950.CrossRefGoogle ScholarPubMed
56.Marais, L, Stein, DJ, Daniels, WM.Exercise increases BDNF levels in the striatum and decreases depressive-like behavior in chronically stressed rats. Metab Brain Dis 2009;24:587–597.CrossRefGoogle ScholarPubMed
57.Gokce, O, Runne, H, Kuhn, A, Luthi-Carter, R.Short-term striatal gene expression responses to brain-derived neurotrophic factor are dependent on MEK and ERK activation. PLoS One 2009;4:5292.CrossRefGoogle ScholarPubMed
58.Duman, RS, Monteggia, LM.A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59: 1116–1127.CrossRefGoogle ScholarPubMed
59.Hall, J, Whalley, HC, Marwick, K et al. Hippocampal function in schizophrenia and bipolar disorder. Psychol Med 2009;7:1–10.Google Scholar
60.Hassel, S, Almeida, JR, Kerr, N et al. Elevated striatal and decreased dorsolateral prefrontal cortical activity in response to emotional stimuli in euthymic bipolar disorder: no associations with psychotropic medication load. Bipolar Disord 2008;10:916–927.CrossRefGoogle ScholarPubMed
61.Hroudova, J, Fisar, Z.Activities of respiratory chain complexes and citrate synthase influenced by pharmacologically different antidepressants and mood stabilizers. Neuroendocrinology Lett 2010;31:336–342.Google ScholarPubMed
62.Burke, WJ, Cj, Kratochvil. Stereoisomers in psychiatry: the case of escitalopra. Prim Care Companion J Clin Psychiatry 2002;4:20–24.Google Scholar
63.Mitchell, PJ, Hogg, S. Beavioural effects of escitalopram predict potent antidepressant activity. Presented at the 7th World Congress of Biological Psychiatry, July 1–6. Berlin, Germany, 2001.Google Scholar
64.Sanchez, C, Hogg, S. The antidepressant effect of citalopram resides in the S-enantiomer (Lu 26-054). Presented at the 55th annual meeting of the Society of Biological Psychiatry, May 11–13. Chicago, IL, 2000.CrossRefGoogle Scholar
65.Mitchell, P, Hogg, S. Escitalopram: rapid antidepressant activity in rats. Presented at the 7th World Congress of Biological Psychiatry, July 1–6. Berlin, Germany, 2001.Google Scholar
66.Pathak, RU, Davey, GP.Complex I and energy theresholds in the brain. Biochim Biophys Acta 2008;1777:777–782.CrossRefGoogle Scholar
67.Barja, G, Herrero, AJ.Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon. J Bioenerg Biomembr 1998;30:235–224.CrossRefGoogle ScholarPubMed
68.Sherer, TB, Betarbet, R, Jh, Kim, Greenamyre, JT.Selective microglial activation in the rat rotenone model of Parkinson's disease. Neurosci Lett 2003;341:87–90.CrossRefGoogle ScholarPubMed
69.Degli, EM.Inhibitors of NADH-ubiquinone reductase: an overview. Biochim Biophys Acta 1998;1364:222–235.CrossRefGoogle Scholar
70.Miyoshi, H.Structure-activity relationships of some complex I inhibitors. Biochim Biophys Acta 1998;1364: 236–244.CrossRefGoogle ScholarPubMed
71.Don, AS, Hogg, PJ.Mitochondria as cancer drug targets. Trends Mol Med 2004;10:372–378.CrossRefGoogle ScholarPubMed
72.Scatena, R, Bottoni, P, Botta, G, Martorana, GE, Giardina, B.The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic. Am J Physiol Cell Physiol 2007;293:C12–C21.CrossRefGoogle ScholarPubMed