Document Type : Research Paper I Open Access I Released under CC BY 4.0 license


1 PhD student, exercise physiology group, the faculty of sport science, university of Mazandaran,Banolsar,Iran.

2 associated professor, Group of exercise physiology, faculty of exercise science, university of Mazandaran, Babolsar, Iran.


The aim of this study was to find answers to these questions: can exercise increase neurogenesis and does neurotrophic factor that is necessary for neurogenesis increase with training?30 rats were divided into four groups: young control, young training, middle-aged control and middle-aged training. The training was performed with overload principle for 6 weeks and 6 sessions per week. Young rats ran with the speed of 27 m/min. and the middle-aged rats with the speed of 20 m/min. for 20 minutes on the first day. The running time increased 2 minutes every day until it reached 60 minutes per day. Elisa method was used to measure the factors and they were analyzed by Tukey post hoc test.There was no significant difference in weight between young groups (sig=0.979) but the difference was significant between middle-aged groups (sig=0.000). Ki67 in young and middle-aged training groups was significantly more than control group (sig=0.002) and (sig=0.037). Midkine did not have a significant increase in the young training group compared with the young control group (sig=0.134). This factor increased in middle-aged training group but this increase was not significant (sig=0.557). The correlation between ki67 and Midkine was significant (r=0.407) (sig=0.029).Continuous training can increase the neurogenesis in young and middle-aged rats. This type of training may be useful to increase neurogenesis and its essentials (i.e. neurotrophic factors).


1.   Kargarfard M, Chitsaz A, Azizi SJJoIMS. Effects of an 8-Week Aquatic Exercise Training on Balance in Patients with Parkinson's Disease. 2012;30(178).
2.   Finch CE, Cohen DMJEn. Aging, metabolism, and Alzheimer disease: review and hypotheses. 1997;143(1):82-102.
3.   Martínez-Cerdeño V, Noctor SC, Espinosa A, Ariza J, Parker P, Orasji S, et al. Embryonic MGE precursor cells grafted into adult rat striatum integrate and ameliorate motor symptoms in 6-OHDA-lesioned rats. 2010;6(3):238-50.
4.   Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. 2012;380(9859):2197-223.
5.   Parkash V, Lindholm P, Peränen J, Kalkkinen N, Oksanen E, Saarma M, et al. The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional. 2009;22(4):233-41.
6.   Ma C-L, Ma X-T, Wang J-J, Liu H, Chen Y-F, Yang YJBbr. Physical exercise induces hippocampal neurogenesis and prevents cognitive decline. 2017;317:332-9.
7.   Lin R, Iacovitti LJBr. Classic and novel stem cell niches in brain homeostasis and repair. 2015;1628:327-42.
8.   Zhao C, Teng EM, Summers RG, Ming G-l, Gage FHJJoN. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. 2006;26(1):3-11.
9.   Kuhn HG, Dickinson-Anson H, Gage FHJJoN. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. 1996;16(6):2027-33.
10. Kee N, Sivalingam S, Boonstra R, Wojtowicz JJJonm. The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. 2002;115(1):97-105.
11. Schinder AF, Poo M-mJTin. The neurotrophin hypothesis for synaptic plasticity. 2000;23(12):639-45.
12. Johansson BBJS. Brain plasticity and stroke rehabilitation: the Willis lecture. 2000;31(1):223-30.
13. Kadomatsu K, Muramatsu TJCl. Midkine and pleiotrophin in neural development and cancer. 2004;204(2):127-43.
14. Fjell AM, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, et al. Minute effects of sex on the aging brain: a multisample magnetic resonance imaging study of healthy aging and Alzheimer's disease. 2009;29(27):8774-83.
15. Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, et al. Aerobic fitness reduces brain tissue loss in aging humans. 2003;58(2):M176-M80.
16. Raz NJNr. Decline and compensation in aging brain and cognition: Promises and constraints. 2009;19(4):411.
17. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, et al. Aerobic exercise training increases brain volume in aging humans. 2006;61(11):1166-70.
18. Arcoverde C, Deslandes A, Rangel A, Rangel A, Pavão R, Nigri F, et al. Role of physical activity on the maintenance of cognition and activities of daily living in elderly with Alzheimer's disease. 2008;66(2B):323-7.
19. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. 2008;300(9):1027-37.
20. Rolland Y, van Kan GA, Vellas BJJotAMDA. Physical activity and Alzheimer's disease: from prevention to therapeutic perspectives. 2008;9(6):390-405.
21. Ploughman M, Austin MW, Glynn L, Corbett DJTsr. The effects of poststroke aerobic exercise on neuroplasticity: a systematic review of animal and clinical studies. 2015;6(1):13-28.
22. Sim Y-J, Kim S-S, Kim J-Y, Shin M-S, Kim C-JJNL. Treadmill exercise improves short-term memory by suppressing ischemia-induced apoptosis of neuronal cells in gerbils. 2004;372(3):256-61.
23. Zhang Y, Zhang P, Shen X, Tian S, Wu Y, Zhu Y, et al. Early exercise protects the blood-brain barrier from ischemic brain injury via the regulation of MMP-9 and occludin in rats. 2013;14(6):11096-112.
24. Song M-K, Seon H-J, Kim I-G, Han J-Y, Choi I-S, Lee S-GJAorm. The effect of combined therapy of exercise and nootropic agent on cognitive function in focal cerebral infarction rat model. 2012;36(3):303-10.
25. Shimada H, Hamakawa M, Ishida A, Tamakoshi K, Nakashima H, Ishida KJBbr. Low-speed treadmill running exercise improves memory function after transient middle cerebral artery occlusion in rats. 2013;243:21-7.
26. Li Y, Luikart BW, Birnbaum S, Chen J, Kwon C-H, Kernie SG, et al. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. 2008;59(3):399-412.
27. Saha B, Peron S, Murray K, Jaber M, Gaillard AJScr. Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury. 2013;11(3):965-77.
28. Borzykh A, Kuzmin I, Mart’ianov A, Borovik A, Sharova A, Tarasova O, et al. Changes of rat respiratory and locomotory muscles during aerobic exercise training in continuous and interval regimens. 2012;57(5):684-9.
29. Siamilis S, Jakus J, Nyakas C, Costa A, Mihalik B, Falus A, et al. The effect of exercise and oxidant–antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats. 2009;47(6):453.
30. Lau YS, Patki G, Das‐Panja K, Le WD, Ahmad SOJEJoN. Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration. 2011;33(7):1264-74.
31. Chilibeck P, Bell G, Farrar R, Martin TJCjop, pharmacology. Higher mitochondrial fatty acid oxidation following intermittent versus continuous endurance exercise training. 1998;76(9):891-4.
32. Shepherd R, Gollnick PJPA. Oxygen uptake of rats at different work intensities. 1976;362(3):219-22.
33. Mathews KJ, Allen KM, Boerrigter D, Ball H, Shannon Weickert C, Double KLJAc. Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers. 2017;16(5):1195-9.
34. Van Praag H, Christie BR, Sejnowski TJ, Gage FHJPotNAoS. Running enhances neurogenesis, learning, and long-term potentiation in mice. 1999;96(23):13427-31.
35. Ma X, Hamadeh MJ, Christie BR, Foster JA, Tarnopolsky MAJPo. Impact of treadmill running and sex on hippocampal neurogenesis in the mouse model of amyotrophic lateral sclerosis. 2012;7(4):e36048.
36. Hauser T, Klaus F, Lipp H-P, Amrein IJBn. No effect of running and laboratory housing on adult hippocampal neurogenesis in wild caught long-tailed wood mouse. 2009;10(1):43.
37. Patten AR, Sickmann H, Hryciw BN, Kucharsky T, Parton R, Kernick A, et al. Long-term exercise is needed to enhance synaptic plasticity in the hippocampus. 2013;20(11):642-7.
38. Inoue K, Okamoto M, Shibato J, Lee MC, Matsui T, Rakwal R, et al. Long-term mild, rather than intense, exercise enhances adult hippocampal neurogenesis and greatly changes the transcriptomic profile of the hippocampus. 2015;10(6):e0128720.
39. Nokia MS, Lensu S, Ahtiainen JP, Johansson PP, Koch LG, Britton SL, et al. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. 2016;594(7):1855-73.
40. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. 2011;108(7):3017-22.
41. Hillman CH, Erickson KI, Kramer AFJNrn. Be smart, exercise your heart: exercise effects on brain and cognition. 2008;9(1):58.
42. Sherwood CC, Subiaul F, Zawidzki TWJJoA. A natural history of the human mind: tracing evolutionary changes in brain and cognition. 2008;212(4):426-54.
43. Dunbar RIJAroA. The social brain: mind, language, and society in evolutionary perspective. 2003;32(1):163-81.
44. Lindholm P. Novel CDNF/MANF protein family: molecular structure, expression and neurotrophic activity. 2009.