The Effect of Endurance Training Before Induction of Alzheimers on Learning Memory and the Changes in Hippocampal Gamma-secretasein Male Wistar Rats

Subject Areas : Journal of Animal Biology

Sajjad Rajabi Amiri ¹ ( Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran )
Alireza Barari ² ( Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran )
Ahmad Abdi ³ ( Department of Sport Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran )

Received: 2020-01-04 Accepted : 2020-05-10 Published : 2020-06-20

Keywords: Hippocampus, Learning and Memory, Alzheimer's Disease, Gamma-secretase,

Abstract :

This study aimed  to investigate the effect of endurance training before induction of Alzheimers on learning, Memory and changes in the hippocampal gamma-secretase in male Wistar rats. For this purpose, 32 8-week-old mature male rats with the avergae weight of 250±17g were randomly divided into two groups of rest (16) and exercise (16) beore Alzheimers induction. After 4 weeks (two 15-min intervals with the speed of 10 m/min in first and second weeks, three 15-min intervals with the speed of 15 m/min in the third week,and four 15-min intervals with the speed of 15 m/min in the fourth week, with 5-min stops), each group was divided into two subgroups: 1. Amyloid beta injection, and 2. no injection. After 72 hours, the animals were killed and their hippocampus was removed. The changes of gamma secretase were measured by Real Time PCR and the obtaiend data analyzed by one-way ANOVA. Morris learning and memory test revealed a significant difference between the time elapsed for finding the platform in different groups on the second (p = 0.001, F = 10.758), third (p ≥ 0.001, p = 0.0057) and the fourth days (p = 0.001, F = 4.846). The time elapsed for finding the platform in the rest-injection group Aβ1-42 was significantly longer than the other gorups on all days (p ≥ 0.001). The results of probe test for spatial memory showed that the time spent in the quadrant of the target circle was significantly different for different groups (p = 0.001, F = 9.25). Also, gamma secretase was significantly decreased in the exercise group compared to rest group after Alzheimers induction (p = 0.001). Aerobic exercise before Alzheimers induction leads to a decrease in gamma-secretase and increase in learning and Memory, and it may lead to hyppocampal plasticity that brings about cognitive and functional benefits.

References:

1. Adlard P.A., Perreau V.M., Pop V., Cotman C.W. 2005. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. Journal of Neuroscience, 25(17): 4217-4221.


2. Aguiar A.S., Castro A.A., Moreira E.L., Glaser V., Santos A.R., Tasca C.I., PredigerR.D. 2011. Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev, 132(11-12): 560-567.


3. Brouillette J., Caillierez R., Zommer N., Alves-Pires C., Benilova I., Blum D., Buée L. 2012. Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid-β1–42 oligomers are revealed in vivo by using a novel animal model. Journal of Neuroscience, 32(23): 7852-7861.


4. Burger C. 2010. Region-specific genetic alterations in the aging hippocampus: implications for cognitive aging. Frontiers in Aging Neuroscience, 2: 1-12.


5. Cotman C.W., Berchtold N.C. 2002 Exercise: a behavioral intervention to enhance brain health and plasticity. Trends in neurosciences, 25(6): 295-301.


6. Cracchiolo J.R., Mori T., Nazian S.J., Tan J., Potter H., Arendash G.W. 2007. Enhanced cognitive activity-over and above social or physical activity-is required to protect Alzheimer’s mice against cognitive impairment, reduce Aβ deposition, and increase synaptic immunoreactivity. Neurobiology of Learning and Memory, 88(3): 277-294.


7. Dao A.T., Zagaar M.A., Alkadhi K.A. 2015. Moderate treadmill exercise protects synaptic plasticity of the dentate gyrus and related signaling cascade in a rat model of Alzheimer’s disease. Molecular Neurobiology, 52(3): 1067-1076.


8. Erickson K.I., Voss M.W., Prakash R. S., Basak C., Szabo A., Chaddock L., Kramer A.F. 2011. Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of USA, 108(7): 3017-3022.


9. Gandy S. 2005. The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. Journal of Clinical Investigation, 115(5): 1121-1129.


10. Ghonsulakandi S.H., Sheikh M., Shasaltaneh M.D., Chopani S., Naghdi N. 2017. The association between effective dose of magnesium and mild compulsive exercise on spatial learning, memory, and motor activity of adult male rats. Biological Trace Element Research, 178(2): 235-245.


11. Haass C., Selkoe D.J. 2007. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide. Nature reviews Molecular Cell Biology, 8(2): 101-112.


12. Hansson O., Zetterberg H., Buchhave P., Andreasson U., Londos E., Minthon L., Blennow K. 2007. Prediction of Alzheimer’s disease using the CSF Aβ42/Aβ40 ratio in patients with mild cognitive impairment. Dementia and Ggeriatric Cognitive Disorders, 23(5): 316-320.


13. Jan A., Hartley D.M., Lashuel H.A. 2010. Preparation and characterization of toxic Aβ aggregates for structural and functional studies in Alzheimer's disease research. Nature Protocols, 5(6): 1186-1209.


14. Jiang S., Li Y., Zhang X., Bu G., Xu H., Zhang Y.W. 2014. Trafficking regulation of proteins in Alzheimer’s disease. Molecular Neurodegeneration, 9(1): 6.


15. Kang E.B., Kwon I.S., Koo J.H., Kim E.J., Kim C.H., Lee J., Cho J.Y. 2013. Treadmill exercise represses neuronal cell death and inflammation during Aβ-induced ER stress by regulating unfolded protein response in aged presenilin 2 mutant mice. Apoptosis, 18(11): 1332-1347.


16. Kang E.B., Cho J.Y. 2014. Effects of treadmill exercise on brain insulin signaling and β-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats. Journal of exercise Nutrition and Biochemistry, 18(1): 89-96.


17. Kodali M., Megahed T., Mishra V., Shuai B., Hattiangady B., Shetty A.K. 2016. Voluntary running exercise-mediated enhanced neurogenesis does not obliterate retrograde spatial memory. Journal of Neuroscience, 36(31): 8112-8122.


18. Liang K.Y., Mintun M.A., Fagan A. M., Goate A.M., Bugg J.M., Holtzman D.M., Morris J.C., Head D. 2010. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Annuals of Neurology, 68(3): 311-318.


19. Liu H.l., Zhao G., Zhang H. 2013. Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice. Behavior and Brain Research, 256: 261-272.


20. Nath S., Agholme L., Kurudenkandy F.R., Granseth B., Marcusson J., Hallbeck M. 2012. Spreading of neurodegenerative pathology via neuron-to-neuron transmission of β-amyloid. Journal of Neuroscience, 32(26): 8767-8777.


21. O'Brien R.J., Wong P.C. 2011. Amyloid precursor protein processing and Alzheimer's disease. Annual review of Neuroscience, 34: 185-204.


22. Parachikova A., Nichol K., Cotman C. 2008. Short-term exercise in aged Tg2576 mice alters neuroinflammation and improves cognition. Neurobiological Disease, 30(1): 121-129.


23. Puzzo D., Sapienza S., Arancio O., Palmeri A. 2008. Role of phosphodiesterase 5 in synaptic plasticity and memory. Neuropsychiatric Disease and Treatment, 4(2): 371-387.


24. Reuben D.B., Judd‐Hamilton L., Harris T.B., Seeman T.E. 2003. The Associations Between Physical Activity and Inflammatory Markers in High‐Functioning Older Persons: MacArthur Studies of Successful Aging. Journal of the American Geriatrics Society, 51(8): 1125-1130.


25. Rolland Y., Abellan van Kan G., Vellas B. 2010. Healthy brain aging: role of exercise and physical activity. Clinics in Geriatric Medicine, 26(1): 75-87.


26. Shahed, A., Ravasi, A. A., Choubineh, S., & Khodadadi, D. 2018. Effect of Four Weeks Exercise Prior Preparation before Alzheimer's Induction on the Levels of Nerve Growth Factor and Beta Amyloid in the Hippocampus of Wistar Male Rats. Journal of Arak University of Medical Sciences, 20(11): 56-66.


27. Soheili Kashani M., Salami M., Rezaei Tavirani M., Talaei Zavareh S.A. 2010. Maze training improves learning in an Alzheimer model of rat. Feyz Journal of Kashan University of Medical Sciences, 14(3): 209-216.


28. Souza L.C., Filho C.B., Goes A.T., Del Fabbro L., de Gomes M.G., Savegnago L., Oliviera M.S., Jesse C.R. 2013. Neuroprotective effect of physical exercise in a mouse model of Alzheimer’s disease induced by β-amyloid 1–40 peptide. Neurotoxicity Research, 24(2): 148-163.


29. Storey E., Cappai R. 1999. The amyloid precursor protein of Alzheimer's disease and the Abeta peptide. Neuropathology and Applied Neurobiology, 25(2): 81-97.


30. Stranahan A.M., Lee K., Becker K.G., Zhang Y., Maudsley S., Martin B., Cutler R.G., Mattson M.P. 2010. Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiology of Aging, 31(11): 1937-1949.


31.  Voss M.W., Prakash R.S., Erickson, K.I., Basak C., Chaddock L., Kim J.S., Kramer A.F. 2010. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Frontiers in Aging Neuroscience, 2: 1-17


32. Yuede C.M., Zimmerman S.D., Dong H., Kling M.J., Bero A.W., Holtzman D.M., Timson B.F., Csernansky J.G. 2009. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease. Neurobiology of Disease, 35(3): 426-432.


33. Zagaar M., Alhaider I., Dao A., Levine A., Alkarawi A., Alzubaidy M., Alkadhi K. 2012. The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiologi cal and molecular evidence. Neurobiology of Disease, 45(3): 1153-1162.