Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-29T07:48:09.621Z Has data issue: false hasContentIssue false

In vitro effect of antipsychotics on brain energy metabolism parameters in the brain of rats

Published online by Cambridge University Press:  22 February 2013

Giselli Scaini
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 (INCT-TM), Porto Alegre, RS, Brazil
Natália Rochi
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 (INCT-TM), Porto Alegre, RS, Brazil
Meline O. S. Morais
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 (INCT-TM), Porto Alegre, RS, Brazil
Débora D. Maggi
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 (INCT-TM), Porto Alegre, RS, Brazil
Bruna T. De-Nês
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 (INCT-TM), Porto Alegre, RS, Brazil
João Quevedo
Affiliation:
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Porto Alegre, RS, 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 (INCT-TM), Porto Alegre, RS, Brazil
*
Emilio L. Streck, Laboratório de Bioenergética, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil. Tel: +554834312539; E-mail: [email protected]

Abstract

Objective

Typical and atypical antipsychotic drugs have been shown to have different clinical, biochemical and behavioural profiles. It is well described that impairment of metabolism, especially in the mitochondria, leads to oxidative stress and neuronal death and has been implicated in the pathogenesis of a number of diseases in the brain. In this context, we investigated the in vitro effect of antipsychotic drugs on energy metabolism parameters in the brain of rats.

Methods

Clozapine (0.1, 0.5 and 1.0 mg/ml), olanzapine (0.1, 0.5 and 1.0 mg/ml) and aripiprazole (0.05, 0.15 and 0.3 mg/ml) were suspended in buffer and added to the reaction medium containing rat tissue homogenates and the respiratory chain complexes, succinate dehydrogenase and creatine kinase (CK) activities were evaluated.

Results

Our results showed that olanzapine and aripriprazole increased the activities of respiratory chain complexes. On the other hand, complex IV activity was inhibited by clozapine, olanzapine and aripriprazole. CK activity was increased by clozapine at 0.5 and 1.0 mg/ml in prefrontal cortex, cerebellum, striatum, hippocampus and posterior cortex of rats. Moreover, olanzapine and aripiprazole did not affect CK activity.

Conclusion

In this context, if the hypothesis that metabolism impairment is involved in the pathophysiology of neuropsychiatric disorders is correct and these results also occur in vivo, we suggest that olanzapine may reverse a possible diminution of metabolism.

Type
Original Articles
Copyright
Scandinavian College of Neuropsychopharmacology 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Albert, KA, Hemmings, HC, Adamo, AIet al.Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia. Arch Gen Psychiatry 2002;59:705712.Google Scholar
2Konradi, C, Eaton, M, MacDonald, ML, Walsh, J, Benes, FM, Heckers, S.Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychiatry 2004;1:300308.CrossRefGoogle Scholar
3Prince, JA, Yassin, MS, Oreland, L.A histochemical demonstration of altered cytochrome oxidase activity in the rat brain by neuroleptics. Eur Neuropsychopharmacol 1998;8:16.Google Scholar
4Angelucci, F, Mathe, AA, Aloe, L.Neurotrophic factors and CNS disorders: findings in rodent models of depression and schizophrenia. Prog Brain Res 2004;146:151165.Google Scholar
5Angelucci, F, Oliviero, A, Pilato, Fet al.Transcranial magnetic stimulation and BDNF plasma levels in amyotrophic lateral sclerosis. Neuroreport 2004;15:717720.Google Scholar
6Duman, RS.Pathophysiology of depression: the concept of synaptic plasticity. Eur Psychiatry 2002;17:306310.Google Scholar
7Duman, RS.Synaptic plasticity and mood disorders. Mol Psychiatry 2002;7:2934.Google Scholar
8Schlattner, U, Wallimann, T.Octamers of mitochondrial creatine kinase isoenzymes differ in stability and membrane binding. J Biol Chem 2000;275:1731417320.Google Scholar
9Velligan, DI, Newcomer, J, Pultz, Jet al.Does cognitive function improve with quetiapine in comparison to haloperidol? Schizophr Res 2002;53:239248.Google Scholar
10Kato, T, Kato, N.Mitochondrial dysfunction in bipolar disorder. Bipolar Disord 2000;2:180190.CrossRefGoogle ScholarPubMed
11Fatemi, SH, Laurence, JA, Araghi-Niknam, Met al.Glial fibrillary acidic protein is reduced in cerebellum of subjects with major depression, but not schizophrenia. Schizophr Res 2004;69:317323.Google Scholar
12Machado-Vieira, R, Lara, DR, Portela, LVet al.Elevated serum S100B protein in drug-free bipolar patients during first manic episode: a pilot study. Eur Neuropsychopharmacol 2002;12:269272.Google Scholar
13Rothermundt, M, Missler, U, Arolt, Vet al.Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. Mol Psychiatry 2001;6:445449.Google Scholar
14Schroeter, ML, Abdul-Khaliq, H, Fruhauf, Set al.Serum S100B is increased during early treatment with antipsychotics and in deficit schizophrenia. Schizophr Res 2003;62:231236.Google Scholar
15Carlson, CD, Cavazzoni, PA, Berg, PH, We, HI, Beasley, CM, Kane, JM.An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine. J Clin Psychiatry 2003;64:898906.Google Scholar
16Burris, KD, Molski, TF, Xu, Cet al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002; 302:381389.Google Scholar
17Jordan, S, Koprivica, V, Chen, R, Tottori, K, Kikuchi, T, Altar, CA.The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol 2002;441:137140.CrossRefGoogle ScholarPubMed
18Beuzen, JN, Taylor, N, Wesnes, K, Wood, A.A comparison of the effects of olanzapine, haloperidol and placebo on cognitive and psychomotor functions in healthy elderly volunteers. J Psychopharmacol 1999;13:152158.Google Scholar
19Calabrese, 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: 739764.Google Scholar
20Madrigal, JL, Olivenza, R, Moro, MAet al.Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 2001;24:420429.Google Scholar
21Fattal, O, Budur, K, Vaughan, AJ, Franco, K.Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics 2006;47:17.Google Scholar
22Wallimann, 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.Google Scholar
23Bessman, SP, Carpenter, CL.The creatine-creatine phosphate energy shuttle. Annu Rev Biochem 1985;54:831865.Google Scholar
24Tsuji, T, Nakamura, Y, Ogata, T, Shibata, T, Kataoka, K.Rapid decrease in ATP content without recovery phase duringglutamate-induced cell death in cultured spinal neurons. Brain Res 1994;62:289292.Google Scholar
25Tomimoto, H, Yamamoto, K, Homburger, HA, Yanagihara, T.Immunoelectron microscopic investigation of creatine kinase BB-isoenzyme after cerebral ischemia in gerbils. Acta Neuropathol 1993;86:447455.Google Scholar
26Aksenov, M, Aksenova, M, Butterfield, DA, Markesbery, WR.Oxidative modification of creatine kinase BB in Alzheimer's disease brain. J Neurochem 2000;74: 25202527.Google Scholar
27David, 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. Mol Brain Res 1998;54:276287.CrossRefGoogle ScholarPubMed
28Gross, WL, Bak, MI, Ingwall, JSet al.Nitric oxide inhibits creatine kinase and regulates rat heart contractile reserve. Proc Natl Acad Sci U S A 1996;93:56045609.Google Scholar
29Streck, EL, Amboni, G, Scaini, Get al.Brain creatine kinase activity in an animal model of mania. Life Sci 2008;82:424429.Google Scholar
30Lee, JM, Grabb, MC, Zipfel, GJ, Choi, DW.Brain tissue responses to ischemia. J Clin Invest 2000;106:723731.Google Scholar
31Blass, JP.Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 2001;66:851856.CrossRefGoogle ScholarPubMed
32Brennan, WA, Bird, ED, Aprille, JR.Regional mitochondrial respiratory activity in Huntington's disease brain. J Neurochem 1985;44:19481950.CrossRefGoogle ScholarPubMed
33Gruno, M, Peet, N, Tein, Aet al.Atrophic gastritis: deficient complex I of the respiratory chain in the mitochondria of corpus mucosal cells. J Gastroenterol 2008;43:780788.Google Scholar
34Schurr, A.Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 2002;41:18.Google Scholar
35Prabakaran, S, Swatton, JE, Ryan, MMet al.Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 2004;9:684697.CrossRefGoogle ScholarPubMed
36Rothermundt, M, Ponath, G, Arolt, V.S100B in schizophrenic psychosis. Int Rev Neurobiol 2004;59:445470.Google Scholar
37Weis, S, Llenos, IC.GFAP-immunopositive astrocytes in schizophrenia. Schizophr Res 2004;67:293295.Google Scholar
38Assis, LC, Scaini, G, Di-Pietro, PBet al.Effect of antipsychotics on creatine kinase activity in rat brain. Basic Clin Pharmacol Toxicol 2007;101:315319.Google Scholar
39Streck, EL, Rezin, GT, Barbosa, LM, Assis, LC, Grandi, E, Quevedo, J.Effect of antipsychotics on succinate dehydrogenase and cytochrome oxidase activities in rat brain. Naunyn Schmiedebergs Arch Pharmacol 2007;376: 127133.Google Scholar
40Polydoro, M, Schröder, N, Lima, MNet al.Haloperidol- and clozapine-induced oxidative stress in the rat brain. Pharmacol Biochem Behav 2004;78:751756.Google Scholar
41Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ.Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265267.Google Scholar
42Cassina, A, Radi, R.Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996;328:309316.Google Scholar
43Fischer, JC, Ruitenbeek, W, Berden, JAet al.Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 1985;153:2336.Google Scholar
44Rustin, P, Chretien, D, Bourgeron, Tet al.Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:3551.Google Scholar
45Hughes, 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.Google Scholar
46Corrêa, C, Amboni, G, Assis, LCet al.Effects of lithium and valproate on hippocampus citrate synthase activity in an animal model of mania. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:887891.CrossRefGoogle Scholar
47Volz, HR, Riehemann, S, Maurer, Iet al.Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: A (31)P chemical shift spectroscopic-imaging study. Biol Psychiatry 2000;47: 954961.CrossRefGoogle ScholarPubMed
48Volz, HP, Rzanny, R, Rossger, Get al.Decreased energy demanding processes in the frontal lobes of schizophrenics due to neuroleptics? A 31Pmagneto-resonance spectroscopic study. Psychiatry Res 1997;76:123129.Google Scholar
49Deicken, RF, Calabrese, G, Merrin, EL, Fein, G, Weiner, MW.Basal ganglia phosphorous metabolism in chronic schizophrenia. Am J Psychiatry 1995;152:126129.Google Scholar
50Andreassen, OA, Ferrante, RJ, Beal, MF, Jorgensen, HA.Oral Dyskinesias and striatal lesions in rats after long-term co-treatment with haloperidol and 3-nitropropionic acid. Neuroscience 1998;87:639648.Google Scholar
51Cadet, JL, Lohr, JB.Possible involvement of free radicals in neuroleptic-induced movement disorders. Evidence from treatment of tardive dyskinesia with vitamin E. Ann N Y Acad Sci 1989;570:176185.CrossRefGoogle ScholarPubMed
52Lohr, JB, Cadet, JL, Lohr, MAet al.Vitamin E in the treatment of tardive dyskinesia: the possible involvement of free radical mechanisms. Schizophr Bull 1988;14:291296.Google Scholar
53Arnaiz, SL, Coronel, MF, Boveris, A.Nitric oxide, superoxide and hydrogen peroxide production in brain mitochondria after haloperidol treatment. Nitric Oxide 1999;3: 235243.Google Scholar
54Adam-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.Google Scholar
55Torres, RL, Torres, ILS, Gamaro, GDet al.Lipid peroxidation and total radical-trapping potential of the lungs of rats submitted to chronic and sub-chronic stress. Braz J Med Biol Res 2004;37:185192.CrossRefGoogle ScholarPubMed
56Khuchua, ZA, Qin, W, Boero, Jet al.Octamer formation and coupling of cardiac sarcomeric mitochondrial creatine kinase are mediated by charged N-terminal residues. J Biol Chem 1998;273:2299022996.Google Scholar
57Wolosker, H, Panizzutti, R, Englender, S.Inhibition of creatine kinase by S-nitrosoglutathione. FEBS Lett 1996;392:274276.Google Scholar