Int J Sports Med 2014; 35(07): 544-550
DOI: 10.1055/s-0033-1357162
Physiology & Biochemistry
© Georg Thieme Verlag KG Stuttgart · New York

Exercise Decreases Susceptibility to Homocysteine Seizures: the Role of Oxidative Stress

D. Hrncic
1   Faculty of Medicine, Institute of Medical Physiology “Richard Burian”, University of Belgrade, Serbia
,
A. Rasic-Markovic
1   Faculty of Medicine, Institute of Medical Physiology “Richard Burian”, University of Belgrade, Serbia
,
J. Lekovic
1   Faculty of Medicine, Institute of Medical Physiology “Richard Burian”, University of Belgrade, Serbia
,
D. Krstic
2   Faculty of Medicine, Department of Medical Chemistry, University of Belgrade, Serbia
,
M. Colovic
3   Institute of Nuclear Sciences Vinca, University of Belgrade, Serbia
,
D. Macut
4   Faculty of Medicine, Institute of Endocrinology, Diabetes and Metabolic Diseases, University of Belgrade, Serbia
,
V. Susic
5   Department of Medical Sciences, Serbian Academy of Sciences and Arts, Belgrade, Serbia
,
D. Djuric
1   Faculty of Medicine, Institute of Medical Physiology “Richard Burian”, University of Belgrade, Serbia
,
O. Stanojlovic
1   Faculty of Medicine, Institute of Medical Physiology “Richard Burian”, University of Belgrade, Serbia
› Author Affiliations
Further Information

Publication History



accepted after revision 02 September 2013

Publication Date:
13 November 2013 (online)

Abstract

The aim of the study was to examine the effects of chronic exercise training on seizures induced by homocysteine thiolactone (HCT) in adult rats. Rats were assigned to: sedentary control; exercise control; sedentary+HCT; exercise+HCT group. Animals in the exercise groups ran 30 min daily on a treadmill for 30 consecutive days (belt speed 20 m/min), while sedentary rats spent the same time on the treadmill (speed 0 m/min). On the 31st day, the HCT groups received HCT (8.0 mmol/kg), while the control groups received vehicle. Afterwards, convulsive behavior and EEG activity were registered. Lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) activity were ascertained in the rat hippocampus. No signs of seizures were registered in sedentary and exercise control rats. Seizure latency was increased, while number of seizure episodes and spike-and-wave discharges (SWD) in EEG were decreased in the exercise+HCT compared to the sedentary+HCT group. Seizure incidence, the severity thereof and duration of SWDs were not significantly different between these groups. Exercise partly prevented increase of lipid peroxidation and decrease of the SOD and CAT activity after HCT administration. These results indicate beneficial effects of exercise in model of HCT-induced seizures in rats, what could be, at least in part, a consequence of improved antioxidant enzymes activity.

 
  • References

  • 1 Aguiar Jr AS, Speck AE, Prediger RD, Kapczinski F, Pinho RA. Downhill training upregulates mice hippocampal and striatal brain-derived neurotrophic factor levels. J Neural Transm 2008; 115: 1251-1255
  • 2 Arida RM, Jesus VA, Cavalheiro EA. Effect of physical exercise on kindling development. Epilepsy Res 1998; 30: 127-132
  • 3 Arida RM, Sanabria ER, da Silva AC, Faria LC, Scorza FA, Cavalheiro EA. Physical training reverts hippocampal electrophysiological changes in rats submitted to the pilocarpine model of epilepsy. Physiol Behav 2004; 30; 83: 165-171
  • 4 Arida RM, Scorza FA, dos Santos NF, Peres CA, Cavalheiro EA. Effect of physical exercise on seizure occurrence in a model of temporal lobe epilepsy in rats. Epilepsy Res 1999; 37: 45-52
  • 5 Aruoma OI, Halliwell B, Laughton MJ, Quinlan GJ, Gutteridge JM. The mechanism of initiation of lipid peroxidation. Evidence against a requirement for an iron(II)-iron(III) complex. Biochem J 1989; 258: 617-620
  • 6 Badawy RA, Harvey AS, Macdonell RA. Cortical hyperexcitability and epileptogenesis: understanding the mechanisms of epilepsy – part 1. J Clin Neurosci 2009; 16: 355-365
  • 7 Beutler E. (ed.). A Manual of Biochemical Methods. New York: Grune and Startton; 1984: 133
  • 8 Cardenas-Rodriguez N, Huerta-Gertrudis B, Rivera-Espinosa L, Montesinos-Correa H, Bandala C, Carmona-Aparicio L, Coballase-Urrutia E. Role of oxidative stress in refractory epilepsy: evidence in patients and experimental models. Int J Mol Sci 2013; 14: 1455-1476
  • 9 Carr DB, Reppert SM, Bullen B, Skrinar G, Beitins I, Arnold M, Rosenblatt M, Martin JB, McArthur JW. Plasma melatonin increases during exercise in women. J Clin Endocrinol Metab 1981; 53: 224-225
  • 10 Cechetti F, Worm PV, Elsner VR, Bertoldi K, Sanches E, Ben J, Siqueira IR, Netto CA. Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat. Neurobiol Learn Mem 2012; 97: 90-96
  • 11 Contarteze RV, de Alencar Mota CS, de Oliveira CA, de Almeida Leme JA, Bottcher LB, de Mello MA, Luciano E. Exercise test and glucose homeostasis in rats treated with alloxan during the neonatal period or fed a high calorie diet. J Diabetes 2009; 1: 65-72
  • 12 Coşkun S, Gönül B, Güzel NA, Balabanlí B. The effects of vitamin C supplementation on oxidative stress and antioxidant content in the brains of chronically exercised rats. Mol Cell Biochem 2005; 280: 135-138
  • 13 da Cunha MJ, da Cunha AA, Ferreira AG, Machado FR, Schmitz F, Lima DD, Delwing D, Mussulini BH, Wofchuk S, Netto CA, Wyse AT. Physical exercise reverses glutamate uptake and oxidative stress effects of chronic homocysteine administration in the rat. Int J Dev Neurosci 2012; 30: 69-74
  • 14 de Lima E, Soares Jr JM, del Carmen Sanabria Garrido Y, Gomes Valente S, Priel MR, Chada Baracat E, Abrão Cavalheiro E, da Graça Naffah-Mazzacoratti M, Amado D. Effects of pinealectomy and the treatment with melatonin on the temporal lobe epilepsy in rats. Brain Res 2005; 1043: 24-31
  • 15 Dubow JS, Kelly JP. Epilepsy in sports and recreation. Sports Med 2003; 33: 499-516
  • 16 Eriksen HR, Ellertsen B, Grønningsaeter H, Nakken KO, Løyning Y, Ursin H. Physical exercise in women with intractable epilepsy. Epilepsia 1994; 35: 1256-1264
  • 17 Folbergrova J. Anticonvulsant action of both NMDA and non-NMDA receptor antagonists against seizure induced by homocysteine in immature rats. Exp Neurol 1997; 145: 442-450
  • 18 Fountain NB, May AC. Epilepsy and athletics. Clin Sports Med 2003; 22: 605-616
  • 19 Getting SJ, Segieth J, Ahmad S, Biggs CS, Whitton PS. Biphasic modulation of GABA release by nitric oxide in the hippocampus of freely moving rats in vivo. Brain Res 1996; 717: 196-199
  • 20 Giusti P, Lipartiti M, Franceschini D, Schiavo N, Floreani M, Manev H. Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. FASEB J 1996; 10: 891-896
  • 21 Harriss DJ, Atkinson G. Update – Ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
  • 22 Herrmann W, Obeid R. Homocysteine: a biomarker in neurodegenerative diseases. Clin Chem Lab Med 2011; 49: 435-441
  • 23 Hoffer LJ. Homocysteine remethylation and trans-sulfuration. Metabolism 2004; 53: 1480-1483
  • 24 Horyd W, Gryziak J, Niedzielska K, Zieliński JJ. Effect of physical exertion on seizure discharges in the EEG of epilepsy patients. Neurol Neurochir Pol 1981; 15: 545-552
  • 25 Hrncić D, Rasić-Marković A, Krstić D, Macut D, Djuric D, Stanojlović O. The role of nitric oxide in homocysteine thiolactone-induced seizures in adult rats. Cell Mol Neurobiol 2010; 30: 219-231
  • 26 Jacoby A, Snape D, Baker GA. Epilepsy and social identity: the stigma of a chronic neurological disorder. Lancet Neurol 2005; 4: 171-178
  • 27 Jakubowski H, Głowacki R. Chemical biology of homocysteine thiolactone and related metabolites. Adv Clin Chem 2011; 55: 81-103
  • 28 Kuijer A. Epilepsy and exercise, electroencephalographical and biochemical studies. Advances in Epileptology: The 10th Epilepsy International Symposium. New York: Raven Press; 1980: 543
  • 29 Lähteinen S, Pitkänen A, Knuuttila J, Törönen P, Castrén E. Brain-derived neurotrophic factor signaling modifies hippocampal gene expression during epileptogenesis in transgenic mice. Eur J Neurosci 2004; 19: 3245-3254
  • 30 Lee MH, Shin MS, Sim YJ, Kim H, Lee HH, Kim CJ, Park C, Hong SP, Cho S. Treadmill exercise enhances nitric oxide synthase expression in the hippocampus of food-deprived rats. Nutrit Res 2005; 25: 771-779
  • 31 Loscher W. Current status and future directions in the pharmacotherapy of epilepsy. Trends Pharmacol Sci 2002; 23: 113-118
  • 32 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin-Phenol reagents. J Biol Chem 1951; 193: 265-275
  • 33 McAuley JW, Long L, Heise J, Kirby T, Buckworth J, Pitt C, Lehman KJ, Moore JL, Reeves AL. A Prospective Evaluation of the Effects of a 12-Week Outpatient Exercise Program on Clinical and Behavioral Outcomes in Patients with Epilepsy. Epilepsy Behav 2001; 2: 592-600
  • 34 Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247: 3170-3175
  • 35 Molteni R, Ying Z, Gomez-Pinilla F. Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci 2002; 16: 1107-1116
  • 36 Nakken KO, Bjørholt PG, Johannessen SI, Løyning T, Lind E. Effect of physical training on aerobic capacity, seizure occurrence, and serum level of antiepileptic drugs in adults with epilepsy. Epilepsia 1990; 3: 88-94
  • 37 Nakken KO, Løyning A, Løyning T, Gløersen G, Larsson PG. Does physical exercise influence the occurrence of epileptiform EEG discharges in children?. Epilepsia 1997; 38: 279-284
  • 38 Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 2006; 580: 2994-3005
  • 39 Ogunyemi AO, Gomez MR, Klass DW. Seizures induced by sexercise. Neurology 1988; 38: 633-634
  • 40 Ozkaya YG, Agar A, Yargiçoglu P, Hacioglu G, Bilmen-Sarikçioglu S, Ozen I, Alicigüzel Y. The effect of exercise on brain antioxidant status of diabetic rats. Diabetes Metab 2002; 28: 377-384
  • 41 Radak Z, Chung HY, Goto S. Systemic adaptation to oxidative challenge induced by regular exercise. Free Radic Biol Med 2008; 44: 153-159
  • 42 Ramsden M, Berchtold NC, Patrick Kesslak J, Cotman CW, Pike CJ. Exercise increases the vulnerability of rat hippocampal neurons to kainate lesion. Brain Res 2003; 971: 239-944
  • 43 Rasić-Marković A, Stanojlović O, Hrncić D, Krstić D, Colović M, Susić V, Radosavljević T, Djuric D. The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol Cell Biochem 2009; 327: 39-45
  • 44 Souza MA, Oliveira MS, Furian AF, Rambo LM, Ribeiro LR, Lima FD, Dalla Corte LC, Silva LF, Retamoso LT, Dalla Corte CL, Puntel GO, de Avila DS, Soares FA, Fighera MR, de Mello CF, Royes LF. Swimming training prevents pentylenetetrazol-induced inhibition of Na+, K+-ATPase activity, seizures, and oxidative stress. Epilepsia 2009; 50: 811-823
  • 45 Stanojlović O, Rasić-Marković A, Hrnčić D, Susić V, Macut D, Radosavljević T, Djuric D. Two types of seizures in homocysteine thiolactone-treated adult rats, behavioral and electroencephalographic study. Cell Mol Neurobiol 2009; 29: 329-339
  • 46 Stewart LS, Leung LS. Hippocampal melatonin receptors modulate seizure threshold. Epilepsia 2005; 46: 473-480
  • 47 Troen AM. The central nervous system in animal models of hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1140-1151
  • 48 Uda M, Ishido M, Kami K, Masuhara M. Effects of chronic treadmill running on neurogenesis in the dentate gyrus of the hippocampus of adult rat. Brain Res 2006; 1104: 64-72
  • 49 Wong J, Wirrell E. Physical activity in children/teens with epilepsy compared with that in their siblings without epilepsy. Epilepsia 2006; 47: 631-639
  • 50 Ziemińska E, Stafiej A, Łazarewicz JW. Role of group I metabotropic glutamate receptors and NMDA receptors in homocysteine-evoked acute neurodegeneration of cultured cerebellar granule neurons. Neurochem Int 2003; 43: 481-492