Effect of treadmill running on social isolation-induced behavioral deficits in male rats

Authors

Abstract

Background and Objective: Social isolation affects the nervous system and leads to behavioral disorders. The aim of this study was to investigate the effect of treadmill running on spatial memory and anxiety and depression behaviors in rats exposed to social isolation.
 
Materials and Methods: In this study, 40 male Wistar rats were divided into 4 groups as follows: 1) Control, 2) Isolation, 3) Treadmill and 4) Isolation-Treadmill. In groups 3 and 4, each rat lived alone in cage for 4 weeks. Groups 2 and 4 were trained 30 min/day, 5 days/week for 4 weeks. At the end of this period, spatial memory, anxiety and depression were evaluated using Morris water maze, elevated plus maze and forced swimming test, respectively.
 
Results: Four weeks of isolation caused spatial memory impairment and anxiety and depression behaviors in the rats. The results of water maze test showed that the time and distance traveled to reach the hidden platform in the Treadmill-Isolation group significantly reduced compared to the Isolation group (P<0.05) and the elapsed time in the target quadrant increased (P<0.05). The results of elevated plus maze test showed that the percentage of entrance to the open arm and the percentage of staying in this arm in the Isolation-Treadmill group increased compared to the Isolation group (P<0.05). Also, the immobilization time of animals in the Isolation-Treadmill group in the forced swimming test was lower than the Isolation group (P<0.05).
 
Conclusion: Treadmill running improves spatial memory and decreases anxiety and depression behaviors in social isolated rats.

Keywords


1. Huong NT, Murakami Y, Tohda M, Watanabe H, Matsumoto K. Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin. Biological and Pharmaceutical Bulletin 2005; 28: 1389-93. 2. Shao Y, Yan G, Xuan Y, Peng H, Huang QJ, Wu R, Xu H. Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus. Behavioural Brain Research 2015; 282: 201-8. 3. Kamal A, Ramakers GM, Altinbilek B, Kas MJ. Social isolation stress reduces hippocampal long-term potentiation: effect of animal strain and involvement of glucocorticoid receptors. Neuroscience 2014; 256: 262-70. 4. Gong Y, Tong L, Yang R, Hu W, Xu X, Wang W, Wang P, Lu X, Gao M, Wu Y, Xu X. Dynamic changes in hippocampal microglia contribute to depressive-like behavior induced by early social isolation. Neuropharmacology 2018; 135: 223-33. 5. Brenes JC, Fornaguera J. The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum. Behavioural Brain Research 2009; 198 (1): 199-205. 6. Sargin D, Oliver DK, Lambe EK. Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels. eLife 2016; 5: e21416. 7. Wallace DL, Han MH, Graham DL, Green TA, Vialou V, Iniguez SD, Cao JL, Kirk A, Chakravarty S, Kumar A, Krishnan V. CREB regulation of nucleus accumbens excitability mediates social isolation–induced behavioral deficits. Nature Neuroscience 2009; 12: 200. 8. Lin S, Li X, Chen YH, Gao F, Chen H, Hu NY, Huang L, Luo ZY, Liu JH, You QL, Yin YN. Social Isolation During Adolescence Induces Anxiety Behaviors and Enhances Firing Activity in BLA Pyramidal Neurons via mGluR5 Upregulation. Molecular Neurobiology 2018; 55 (6): 5310-20. 9. Murínová J, Hlaváčová N, Chmelová M, Riečanský I. The evidence for altered BDNF expression in the brain of rats reared or housed in social isolation: a systematic review. Frontiers in Behavioral Neuroscience 2017; 11: 101. 10. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends in Neurosciences 2002; 25 (6): 295-301. 11. Rybak LP, Somani SM, Ravi R. Effect of exercise training on antioxidant system in brain regions of rat. Pharmacology Biochemistry & Behavior 1995; 50 (4): 635-9. 12. da Silva SG, Simões PS, Mortara RA, Scorza FA, Cavalheiro EA, da Graça Naffah-Mazzacoratti M, et al. Exercise-induced hippocampal anti-inflammatory response in aged rats. Journal of Neuroinflammation 2013; 10 (1): 827. 13. Uysal N, Tugyan K, Kayatekin BM, Acikgoz O, Bagriyanik HA, Gonenc S, et al. The effects of regular aerobic exercise in adolescent period on hippocampal neuron density, apoptosis and spatial memory. Neuroscience Letters 2005; 383 (3): 241-5. 14. Radahmadi M, Hosseini N, Alaei H. Effect of exercise, exercise withdrawal, and continued regular exercise on excitability and long-term potentiation in the dentate gyrus of hippocampus. Brain Research 2016; 1653: 8-13. 15. Lin C, Wu CJ, Wei IH, Tsai MH, Chang NW, Yang TT, et al. Chronic treadmill running protects hippocampal neurons from hypobaric hypoxia-induced apoptosis in rats. Neuroscience 2013; 231: 216-24. 16. Leraci A, Mallei A, Popoli M. Social isolation stress induces anxious-depressive-like behavior and alterations of neuroplasticity-related genes in adult male mice. Neural Plasticity 2016; 2016: 1-13. 17. Bigdeli Y, Asle-Rousta M, Rahnema M. Effects of Limonene on Chronic Restraint Stress-Induced Memory Impairment and Anxiety in Male Rats. Neurophysiology 2019; 51: 1-7. 18. Fadaei S, Asle-Rousta M. Anxiolytic and antidepressant effects of cinnamon (Cinnamomum verum) extract in rats receiving lead acetate. Scientific Journal of Kurdistan University of Medical Sciences 2017; 22: 31-39. 19. Ibi D, Takuma K, Koike H, Mizoguchi H, Tsuritani K, Kuwahara Y, et al. Social isolation rearing‐induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion‐related behaviors in juvenile mice. Journal of Neurochemistry 2008; 105 (3): 921-32. 20. Lukkes JL, Watt MJ, Lowry CA, Forster GL. Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents. Frontiers in Behavioral Neuroscience 2009; 3: 18. 21. Okudan N, Belviranlı M. Long-term voluntary exercise prevents post-weaning social isolation-induced cognitive impairment in rats. Neuroscience 2017; 360: 1-8. 22. Cho JW, Jung SY, Lee SW, Lee SJ, Seo TB, Kim YP, et al. Treadmill exercise ameliorates social isolation-induced depression through neuronal generation in rat pups. Journal of Exercise Rehabilitation 2017; 13 (6): 627-633. 23. Hong YP, Lee HC, Kim HT. Treadmill exercise after social isolation increases the levels of NGF, BDNF, and synapsin I to induce survival of neurons in the hippocampus, and improves depression-like behavior. Journal of Exercise Nutrition and Biochemistry 2015; 19 (1): 11. 24. Cevik OS, Sahin L, Tamer L. Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning. Life science 2018; 200: 126-33. 25. Lu Y, Dong Y, Tucker D, Wang R, Ahmed ME, Brann D, et al. Treadmill exercise exerts neuroprotection and regulates microglial polarization and oxidative stress in a streptozotocin-induced rat model of sporadic Alzheimer’s disease. Journal of Alzheimer's Disease 2017; 56 (4): 1469-84. 26. Sim YJ, Kim SS, Kim JY, Shin MS, Kim CJ. Treadmill exercise improves short-term memory by suppressing ischemia-induced apoptosis of neuronal cells in gerbils. Neuroscience Letters 2004; 372: 256-61. 27. Liu HL, Zhao G, Cai K, Zhao HH. Treadmill exercise prevents decline in spatial learning and memory in APP/PS1 transgenic mice through improvement of hippocampal long-term potentiation. Behavioral Brain Research 2011; 218: 308-14. 28. Kim G, Kim E. Effects of treadmill training on limb motor function and acetylcholinesterase activity in rats with stroke. Journal of Physical Therapy Science 2013; 25: 1227-30. 29. Maejima H, Kanemura N, Kokubun T, Murata K, Takayanagi K. Effects of Aging and Treadmill Exercise on the Expression of Neurotrophin and Glutamate Receptors in the Hippocampus. Federation of American Societies for Experimental Biology Journal 2015; 29: 1055-6. 30. Mazur FG, Oliveira LF, Cunha MP, Rodrigues AL, Pértile RA, Vendruscolo LF, Izídio GS. Effects of physical exercise and social isolation on anxiety-related behaviors in two inbred rat strains. Behavioural Processes 2017; 142: 70-8. 31. Salim S, Sarraj N, Taneja M, Saha K, Tejada-Simon MV, Chugh G. Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats. Behavioral Brain Research 2010; 208: 545-52. 32. Jia J, Hu YS, Wu Y, Liu G, Yu HX, Zheng QP, et al. Pre-ischemic treadmill training affects glutamate and gamma aminobutyric acid levels in the striatal dialysate of a rat model of cerebral ischemia. Life Science 2009; 84: 505-11. 33. Park JK, Lee SJ, Oh CS. Treadmill exercise exerts ameliorating effect on isolation-induced depression via neuronal activation. Journal of Exercise Rehabilitation 2013; 9: 234. 34. Ji ES, Lee JM, Kim TW, Kim YM, Kim YS, Kim K. Treadmill exercise ameliorates depressive symptoms through increasing serotonin expression in postpartum depression rats. Journal of Exercise Rehabilitation 2017; 13: 130. 35. 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: 1607-18. 36. Wang LR, Baek SS. Treadmill exercise activates PI3K/Akt signaling pathway leading to GSK-3β inhibition in the social isolated rat pups. Journal of Exercise Rehabilitation 2018; 14: 4. 37. Lee TH, Kim K, Shin MS, Kim CJ, Lim BV. Treadmill exercise alleviates chronic mild stress-induced depression in rats. Journal of Exercise Rehabilitation 2015; 11: 303. 38. 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 and Behavior 2014; 130: 47-53.