Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license
Authors
1 PhD Student of Biochemistry and Exercise Metabolism, Faculty of Physical Education and Sport Sciences, Islamic Azad University, Central Tehran Branch, Tehran, Iran
2 Professor, Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University,Tehran, Iran
Abstract
The aim of this study was to determine the effect of four weeks of voluntary running on running wheel (RW) in adolescence on depression and its effect on oxidative stress in the cerebellum. For this purpose, 24 male rats were randomly divided into 3 groups: control, separated from mother (MS) and separated from mother and running wheel (MS + RW). MS and MS + RW rats were separated from their mothers from postnatal day (PND) 2 to 14 for 180 min. per day. Then, each 4 rats per cage were kept until the 28th day. MS + RW group had access to the running wheel 24 hours a day from the 28th day. At PND 60, depressive-like behaviors were assessed by Open Field Test (OPT), Sucrose Preference Test (SPT), Forced Swimming Test (FST) and Splash test. Biomarker of oxidative stress including mitochondrial reactive oxygen species (ROS) in the cerebellum tissue was also measured. The results showed that voluntary running significantly neutralized depression-like behaviors induced by the maternal separation stress and reduced oxidative stress. Also, the results showed that voluntary running could be useful as a non-pharmacological treatment for depression.
Keywords
1. Costello EJ, Egger HL, Angold A. The developmental epidemiology of anxiety disorders: phenomenology, prevalence, and comorbidity. Child and Adolescent Psychiatric Clinics. 2005;14(4):631-48.
2. Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Annu Rev Physiol. 2005;67:259-84.
3. Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. American Journal of Psychiatry. 2001;158(4):575-81.
4. Rao U, Chen L-A, Bidesi AS, Shad MU, Thomas MA, Hammen CL. Hippocampal changes associated with early-life adversity and vulnerability to depression. Biological psychiatry. 2010;67(4):357-64.
5. Sadeghi M, Peeri M, Hosseini M-J. Adolescent voluntary exercise attenuated hippocampal innate immunity responses and depressive-like behaviors following maternal separation stress in male rats. Physiology & behavior. 2016;163:177-83.
6. Marco EM, Llorente R, López-Gallardo M, Mela V, Llorente-Berzal Á, Prada C, et al. The maternal deprivation animal model revisited. Neuroscience & Biobehavioral Reviews. 2015;51:151-63.
7. Faure J, Uys JD, Marais L, Stein DJ, Daniels WM. Early maternal separation followed by later stressors leads to dysregulation of the HPA-axis and increases in hippocampal NGF and NT-3 levels in a rat model. Metabolic brain disease. 2006;21(2-3):172-9.
8. Hofer MA. Cardiac rate regulated by nutritional factor in young rats. Science. 1971;172(3987):1039-41.
9. Amini-Khoei H, Amiri S, Shirzadian A, Haj-Mirzaian A, Alijanpour S, Rahimi-Balaei M, et al. Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: involvement of the opioid system. Epilepsy & Behavior. 2015;52:37-41.
10. Haj-Mirzaian A, Amiri S, Amini-Khoei H, Rahimi-Balaei M, Kordjazy N, Olson CO, et al. Attenuation of oxidative and nitrosative stress in cortical area associates with antidepressant-like effects of tropisetron in male mice following social isolation stress. Brain research bulletin. 2016;124:150-63.
11. Picard M, Juster R-P, McEwen BS. Mitochondrial allostatic load puts the'gluc'back in glucocorticoids. Nature Reviews Endocrinology. 2014;10(5):303.
12. Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J, et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology. 2001;24(4):420.
13. Beal MF. Mitochondria, free radicals, and neurodegeneration. Current opinion in neurobiology. 1996;6(5):661-6.
14. Navarro A, Gomez C, López-Cepero JM, Boveris A. Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. American journal of physiology-regulatory, integrative and comparative physiology. 2004;286(3):R505-R11.
15. Daniels WM, Marais L, Stein DJ, Russell VA. Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation. Experimental physiology. 2012;97(2):239-47.
16. Patki G, Li L, Allam F, Solanki N, Dao AT, Alkadhi K, et al. Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder. Physiology & behavior. 2014;130:47-53.
17. Kalani R, Judge S, Carter C, Pahor M, Leeuwenburgh C. Effects of caloric restriction and exercise on age-related, chronic inflammation assessed by C-reactive protein and interleukin-6. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2006;61(3):211-7.
18. Somani S, Husain K, Diaz-Phillips L, Lanzotti D, Kareti K, Trammell G. Interaction of exercise and ethanol on antioxidant enzymes in brain regions of the rat. Alcohol. 1996;13(6):603-10.
19. Brocardo PS, Boehme F, Patten A, Cox A, Gil-Mohapel J, Christie BR. Anxiety-and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise. Neuropharmacology. 2012;62(4):1607-18.
20. Miladi-Gorji H, Rashidy-Pour A, Fathollahi Y. Anxiety profile in morphine-dependent and withdrawn rats: effect of voluntary exercise. Physiology & behavior. 2012;105(2):195-202.
21. Cryan JF, Holmes A. Model organisms: the ascent of mouse: advances in modelling human depression and anxiety. Nature reviews Drug discovery. 2005;4(9):775.
22. Amiri S, Haj-Mirzaian A, Rahimi-Balaei M, Razmi A, Kordjazy N, Shirzadian A, et al. Co-occurrence of anxiety and depressive-like behaviors following adolescent social isolation in male mice; possible role of nitrergic system. Physiology & behavior. 2015;145:38-44.
23. Wallace DL, Han M-H, Graham DL, Green TA, Vialou V, Iniguez SD, et al. CREB regulation of nucleus accumbens excitability mediates social isolation–induced behavioral deficits. Nature neuroscience. 2009;12(2):200.
24. Shaki F, Hosseini M-J, Ghazi-Khansari M, Pourahmad J. Toxicity of depleted uranium on isolated rat kidney mitochondria. Biochimica et Biophysica Acta (BBA)-General Subjects. 2012;1820(12):1940-50.
25. Jafarian I, Eskandari MR, Mashayekhi V, Ahadpour M, Hosseini M-J. Toxicity of valproic acid in isolated rat liver mitochondria. Toxicology mechanisms and methods. 2013;23(8):617-23.
26. Aksu I, Topcu A, Camsari UM, Acikgoz O. Effect of acute and chronic exercise on oxidant–antioxidant equilibrium in rat hippocampus, prefrontal cortex and striatum. Neuroscience letters. 2009;452(3):281-5.
27. Campbell EJ, James MH, Hodgson DM, Dayas CV, editors. Effects of maternal separation on brain stress systems: Modulation by voluntary exercise in male rats. International Journal of Exercise Science: Conference Proceedings; 2013.
28. Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ, editors. Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Seminars in cell & developmental biology; 2011: Elsevier.
29. Olson AK, Eadie BD, Ernst C, Christie BR. Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus. 2006;16(3):250-60.
30. Ernst M, Romeo RD, Andersen SL. Neurobiology of the development of motivated behaviors in adolescence: a window into a neural systems model. Pharmacology Biochemistry and Behavior. 2009;93(3):199-211.
31. Patki G, Solanki N, Atrooz F, Ansari A, Allam F, Jannise B, et al. Novel mechanistic insights into treadmill exercise based rescue of social defeat-induced anxiety-like behavior and memory impairment in rats. Physiology & behavior. 2014;130:135-44.
32. Dishman RK, Renner KJ, White-Welkley JE, Burke K, Bunnell BN. Treadmill exercise training augments brain norepinephrine response to familiar and novel stress. Brain research bulletin. 2000;52(5):337-42.
33. Haj-Mirzaian A, Amiri S, Kordjazy N, Momeny M, Razmi A, Rahimi-Balaei M, et al. Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic–pituitary–adrenal axis function. Neuroscience. 2016;315:271-85.
34. Blomgren K, Hagberg H. Free radicals, mitochondria, and hypoxia–ischemia in the developing brain. Free radical biology and medicine. 2006;40(3):388-97.
35. Ikonomidou C, Kaindl AM. Neuronal death and oxidative stress in the developing brain. Antioxidants & redox signaling. 2011;14(8):1535-50.
36. Alano CC, Tran A, Tao R, Ying W, Karliner JS, Swanson RA. Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes. Journal of neuroscience research. 2007;85(15):3378-85.
37. Sonei N, Amiri S, Jafarian I, Anoush M, Rahimi-Balaei M, Bergen H, et al. Mitochondrial dysfunction bridges negative affective disorders and cardiomyopathy in socially isolated rats: pros and cons of fluoxetine. The World Journal of Biological Psychiatry. 2017;18(1):39-53.
38. Huang J, Philbert MA. Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells. Brain research. 1995;680(1-2):16-22.
39. Beiswanger C, Diegmann M, Novak R, Philbert M, Graessle T, Reuhl K, et al. Developmental changes in the cellular distribution of glutathione and glutathione S-transferases in the murine nervous system. Neurotoxicology. 1995;16(3):425-40.
40. Sun X, Shih AY, Johannssen HC, Erb H, Li P, Murphy TH. Two-photon imaging of glutathione levels in intact brain indicates enhanced redox buffering in developing neurons and cells at the cerebrospinal fluid and blood-brain interface. Journal of Biological Chemistry. 2006;281(25):17420-31.
41. Vetulani J. Early maternal separation: a rodent model of depression and a prevailing human condition. Pharmacological reports. 2013;65(6):1451-61.
42. Ji LL, Katz A, Fu R, Griffiths M, Spencer M. Blood glutathione status during exercise: effect of carbohydrate supplementation. Journal of Applied Physiology. 1993;74(2):788-92.
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