Document Type : Research Paper

Authors

1 . PhD Student of Sports Physiology, Kish International Campus, University of Tehran

2 Professor of Sports Physiology, University of Tehran

3 Associate Professor of Sports Physiology, Kish International Campus, University of Tehran

Abstract

Alzheimer's disease is a progressive disorder of the nervous system. Aβ-induced degradation reactions in the CNS result in neurotrophic factor abnormalities, which may in turn facilitate the development of amyloid pathology. The effects of exercise on these factors have been taken into account, however, an understanding of how it works needs further investigation. Therefore, the purpose of this study was to investigate the effect of aerobic training on Trk-B, PKC and AKT in hippocampus of male rats with Alzheimer’s Disease. In this experimental study, 36 adult male rats (8 weeks) with an average weight of 195 ± 20 g were randomly divided into 3 groups: Alzheimer's Disease (AD), Alzheimer's Disease + exercise training (ADT), and control (C). The induction of Alzheimer's disease was induced by intrahippocampal injection of Aβ1-42. Aerobic exercise was performed for 4 weeks, 5 sessions per week. 24 hours after the last training session, animals were either subjected to behavioral testing or killed, and their hippocampus was extracted for further experiments. One-way ANOVA was used to analyze the data. The results showed that the ADT rats spend significantly more time in the target quadrant compared to the AD group in the probe test (p ≤ 0.05). Also, Trk-B, PKC and AKT levels decrease following injection of Aβ1-42 (p <0.001). Aerobic exercise increased Trk-B, PKC and AKT levels compared to AD rats (p≤0.05). Therefore, aerobic exercise seems to help improve the spatial memory by activating the TrkB- PKC-AKT signaling pathway.

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Main Subjects

  1. Rolland Y, van Kan GA, Vellas B. Healthy brain aging: role of exercise and physical activity. Clinics in geriatric medicine. 2010;26(1):75-87.
  2. Grundke-Iqbal I, Iqbal K, Tung Y-C, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences. 1986;83(13):4913-7.
  3. Klein R, Lamballe F, Bryant S, Barbacid M. The trkB tyrosine protein kinase is a receptor for neurotrophin-4. Neuron. 1992;8(5):947-56.
  4. Reichardt LF. Neurotrophin-regulated signalling pathways. Philosophical Transactions of the Royal Society of London B: Biological Sciences. 2006;361(1473):1545-64.
  5. Chen Z, Simmons MS, Perry RT, Wiener HW, Harrell LE, Go RC. Genetic association of neurotrophic tyrosine kinase receptor type 2 (NTRK2) with Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2008;147(3):363-9.
  6. Vaynman S, Ying Z, Gomez‐Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. European Journal of Neuroscience. 2004;20(10):2580-90.
  7. Lin T-W, Shih Y-H, Chen S-J, Lien C-H, Chang C-Y, Huang T-Y, et al. Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer’s disease (APP/PS1) transgenic mice. Neurobiology of learning and memory. 2015; 118:189-97.
  8. Klintsova AY, Dickson E, Yoshida R, Greenough WT. Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise. Brain research. 2004;1028(1):92-104.
  9. Gupta VK, You Y, Gupta VB, Klistorner A, Graham SL. TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. International journal of molecular sciences. 2013;14(5):10122-42.

 

  1. Khorshidahmad T, Tabrizian K, Vakilzadeh G, Nikbin P, Moradi S, Hosseini-Sharifabad A, et al. Interactive effects of a protein kinase AII inhibitor and testosterone on spatial learning in the Morris water maze. Behavioural brain research. 2012;228(2):432-9.
  2. Prakash A, Medhi B, Chopra K. Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-β induced experimental model of Alzheimer's disease. Pharmacology Biochemistry and Behavior. 2013;110:46-57.
  3. Stephan A, Laroche S, Davis S. Generation of aggregated β-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits. Journal of Neuroscience. 2001;21(15):5703-14.
  4. Dao AT, Zagaar MA, Alkadhi KA. Moderate treadmill exercise protects synaptic plasticity of the dentate gyrus and related signaling cascade in a rat model of Alzheimer’s disease. Molecular neurobiology. 2015;52(3):1067-76.
  5. Zagaar M, Alhaider I, Dao A, Levine A, Alkarawi A, Alzubaidy M, et al. The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence. Neurobiology of disease. 2012;45(3):1153-62.
  6. Jan A, Hartley DM, Lashuel HA. Preparation and characterization of toxic Aβ aggregates for structural and functional studies in Alzheimer's disease research. Nature protocols. 2010;5(6):1186-209.
  7. Zhang J, Guo J, Zhao X, Chen Z, Wang G, Liu A, et al. Phosphodiesterase-5 inhibitor sildenafil prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in APP/PS1 transgenic mice. Behavioural brain research. 2013; 250:230-7.
  8. Puzzo D, Sapienza S, Arancio O, Palmeri A. Role of phosphodiesterase 5 in synaptic plasticity and memory. Neuropsychiatric disease and treatment. 2008;4(2):371.
  9. Bariohay B, Lebrun B, Moyse E, Jean A. Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex. Endocrinology. 2005;146(12):5612-20.
  10. Gottschalk WA, Jiang H, Tartaglia N, Feng L, Figurov A, Lu B. Signaling mechanisms mediating BDNF modulation of synaptic plasticity in the hippocampus. Learning & Memory. 1999;6(3):243-56.
  11. Liu YF, Chen Hi, Wu CL, Kuo YM, Yu L, Huang AM, et al. Differential effects of treadmill running and wheel running on spatial or aversive learning and memory: roles of amygdalar brain‐derived neurotrophic factor and synaptotagmin I. The Journal of physiology. 2009;587(13):3221-31.
  12. Hosseini SE, Mojtahedi S, Kordi MR, Shabkhiz F, Fallah Omran S. Effect of short term and light forced treadmill running on BDNF and TrkB in the hippocampus of adult wistar male rats. Razi Journal of Medical Sciences. 2012;19(101):61-7.
  13. Gómez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. Journal of neurophysiology. 2002;88(5):2187-95.
  14. Chae C, Jung S, An S, Park B, Wang S, Cho I, et al. RETRACTED: Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Elsevier; 2009.
  15. Segura-Aguilar J, Kostrzewa RM. Neurotoxins and neurotoxicity mechanisms. An overview. Neurotoxicity research. 2006;10(3-4):263-85.
  16. Reilly MM, Shy ME. Diagnosis and new treatments in genetic neuropathies. Journal of Neurology, Neurosurgery & Psychiatry. 2009;80(12):1304-14.