| Peer-Reviewed

Effect of Different Exercise Intensity Preconditioning on Global Ischemia-Induced Neuronal Death and Expression of Gadd45β and DNA-PKcs in Rats

Received: 5 August 2020     Accepted: 21 August 2020     Published: 10 September 2020
Views:       Downloads:
Abstract

Background Acute ischemic stroke causes long-term neurological and neurobehavioral dysfunctions. With the development of clinical medicine, the importance of pre-ischemic exercise intervention has been gradually recognized, but its mechanism remains to be further explored. Objective This study investigates the effects of different exercise intensity preconditioning in changes of hippocampal neurons and the expression of Gadd45β and DNA-PKcs in the hippocampal region after cerebral ischemia-reperfusion in rats. Method 160 SD rats were divided into control group (n=40), cerebral ischemia reperfusion group (I/R group, n=40), middle intensity exercise preconditioning group (EI 1+I/R group, n=40), high intense exercise preconditioning group (EI 2+I/R group, n=40). Stroke was induced by improved Pulsinelli four blood vessel blocking after exercise preconditioning. Morphological changes of neurons in the hippocampal region of rats were observed by HE staining at 6 h, 1d, 3d and 7d after ischemia in each group. Immunohistochemistry method was used to detect the expression of Gadd45β and DNA-PKcs in hippocampus CA1. The mRNA level of Gadd45β and DNA-PKcs in hippocampal CA1 was detected by Real Time PCR. Results Compared with I/R group, the neuronal cell necrosis of was alleviated in EI 1+I/R group, but more serious in EI 2+I/R group; The expression of Gadd45β and DNA-PKcs were significantly higher in the EI 1+ I/R group, but lower in EI 2+I/R group (P<0.01). Conclusion Moderate intensity exercise preconditioning can improve the survival of neurons after cerebral ischemia-reperfusion injury in rats. However, high-intensity motor preconditioning increased the damage and loss of neurons, and its mechanism may be related to the regulation of the expression of Gadd45β and DNA-PKcs in the hippocampus of cerebral ischemia-reperfusion rats, thus protecting and promoting the function of DNA repair system.

Published in Biomedical Sciences (Volume 6, Issue 3)
DOI 10.11648/j.bs.20200603.14
Page(s) 61-66
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Exercise, Cerebral Ischemia/Reperfusion, Gadd45β, DNA-PKcs

References
[1] Feigin V L, Nguyen G, CERCY K, et al. Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016 [J]. New England Journal of Medicine, 2018, 379 (25): 2429-2437.
[2] Jianping Jia, Shengdi Chen. Neurology [M], Beijing: People's Medical Publishing House, 2018: 194-207.
[3] Kassebaum N J, Smith A G C, Bernabé E, et al. Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990–2015: A SystEIatic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors [J]. Journal of Dental Research, 2017, 96 (4): 380-387.
[4] Ciobanu L G, Ferrari A J, Erskine H E, et al. The prevalence and burden of mental and substance use disorders in Australia: Findings from the Global Burden of Disease Study 2015 [J]. Australian & New Zealand Journal of Psychiatry, 2018, 52 (5): 483-490.
[5] Hongyu Li, Qiang Tang, Luwen Zhu, et al. Effect of Exercise Preconditioning on Cell Apoptosis and Expression of Mitochondrial ATP-sensitive Potassium Channels Protein in Rats after Cerebral Ischemia-reperfusion [J]. Chinese Journal of Rehabilitation Theory and Practice, 2018, 24 (5): 497-501.
[6] Xing Y, Yang SD, Dong F, Wang MM, Feng YS, Zhang F. The beneficial role of early exercise training following stroke and possible mechanisms. Life Sci. 2018 Apr 1; 198: 32-37.
[7] Zhumei Sun, Yaning Zhao, Jianmin Li, et al. Effect of Different Exercise Intensity Preconditioning on Expression of Growth Associated Protein-43 and Nogo-A in Rats with Cerebral Ischemia/Reperfusion [J]. Chinese Journal of Anatomy, 2018, 41 (1): 40-44.
[8] Laura Narciso, Eleonora Parlanti, Mauro Racaniello, et al. The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease [J]. Neural Plast. 2016: 3619274.
[9] Cho CH, Byun HR, Jover-Mengual T, et al. Gadd45βb Acts as Neuroprotective Effector in Global Ischemia-Induced Neuronal Death [J]. Int Neurourol J 2019 Feb; 23.
[10] Enriquez-Rios V, Dumitrache LC, Downing SM, et al. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis [J]. J. Neurosci. 2017 01 25; 37 (4).
[11] Elsaid FH, Khalil AA, Ibrahim EI, Mansour A, Hussein AM. Effects of exercise and stevia on renal ischemia/reperfusion injury in rats. Acta Sci Pol Technol Aliment. 2019 Jul-Sep; 18 (3): 317-332.
[12] Wu C, Yang L, Tucker D, Dong Y, Zhu L, Duan R, Liu TC, Zhang Q. Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer's Rat Model. Med Sci Sports Exerc. 2018 May; 50 (5): 945-956.
[13] Linder SM, Rosenfeldt AB, Davidson S, et al. Forced, Not Voluntary, Aerobic Exercise Enhances Motor Recovery in Persons With Chronic Stroke [J]. Neurorehabil Neural Repair. 2019 Aug; 33 (8): 681-690.
[14] Luo L, Li C, Deng Y, et al. High-Intensity Interval Training on Neuroplasticity, Balance between Brain-Derived Neurotrophic Factor and Precursor Brain-Derived Neurotrophic Factor in Poststroke Depression Rats [J]. J Stroke Cerebrovasc Dis. 2019 Mar; 28 (3): 672-682.
[15] Andrews SC, Curtin D, Hawi Z, et al. ntensity Matters: High-intensity Interval Exercise Enhances Motor Cortex Plasticity More Than Moderate Exercise [J]. Cereb Cortex. 2020 Jan 10; 30 (1): 101-112.
[16] Fengwu Li, 1 Xiaokun Geng, 1, 2, 3, * Christian Huber, et al. In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats [J]. Front Cell Neurosci. 2020; 14: 186.
[17] Brivio P, Sbrini G, Riva MA, et al. Acute Stress Induces Cognitive Improvement in the Novel Object Recognition Task by Transiently Modulating Bdnf in the Prefrontal Cortex of Male Rats [J]. Cell. Mol. Neurobiol. 2020 Aug; 40 (6).
[18] Xu QH, Song BJ, Liu D, et al. The MKK7 inhibitor peptide Gadd45β -I attenuates ER stress-induced mitochondrial dysfunction in HT22 cells: Involvement of JNK-Wnt pathway [J]. Brain Res. 2018 07 15; 1691.
[19] Vanessa Enriquez-Rios, Lavinia C. Dumitrache, Susanna M. Downing, et al. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis [J]. J Neurosci. 2017 Jan 25; 37 (4): 893–905.
[20] Effects of ALK5 Signaling Pathway on Cerebral Plasticity and Motor Function Recovery after Cerebral Ischemia/Reperfusion Injury [D]. Chongqing medical university, 2019.5.
[21] James N. Cobley, Nikos V. Margaritelis, James P. Morton, et al. The basic chEIistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay [J]. Front Physiol. 2015, 6: 182.
Cite This Article
  • APA Style

    Zhumei Sun, Xu Zhao, Jianmin Li, Yaning Zhao, Changxiang Chen. (2020). Effect of Different Exercise Intensity Preconditioning on Global Ischemia-Induced Neuronal Death and Expression of Gadd45β and DNA-PKcs in Rats. Biomedical Sciences, 6(3), 61-66. https://doi.org/10.11648/j.bs.20200603.14

    Copy | Download

    ACS Style

    Zhumei Sun; Xu Zhao; Jianmin Li; Yaning Zhao; Changxiang Chen. Effect of Different Exercise Intensity Preconditioning on Global Ischemia-Induced Neuronal Death and Expression of Gadd45β and DNA-PKcs in Rats. Biomed. Sci. 2020, 6(3), 61-66. doi: 10.11648/j.bs.20200603.14

    Copy | Download

    AMA Style

    Zhumei Sun, Xu Zhao, Jianmin Li, Yaning Zhao, Changxiang Chen. Effect of Different Exercise Intensity Preconditioning on Global Ischemia-Induced Neuronal Death and Expression of Gadd45β and DNA-PKcs in Rats. Biomed Sci. 2020;6(3):61-66. doi: 10.11648/j.bs.20200603.14

    Copy | Download

  • @article{10.11648/j.bs.20200603.14,
      author = {Zhumei Sun and Xu Zhao and Jianmin Li and Yaning Zhao and Changxiang Chen},
      title = {Effect of Different Exercise Intensity Preconditioning on Global Ischemia-Induced Neuronal Death and Expression of Gadd45β and DNA-PKcs in Rats},
      journal = {Biomedical Sciences},
      volume = {6},
      number = {3},
      pages = {61-66},
      doi = {10.11648/j.bs.20200603.14},
      url = {https://doi.org/10.11648/j.bs.20200603.14},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20200603.14},
      abstract = {Background Acute ischemic stroke causes long-term neurological and neurobehavioral dysfunctions. With the development of clinical medicine, the importance of pre-ischemic exercise intervention has been gradually recognized, but its mechanism remains to be further explored. Objective This study investigates the effects of different exercise intensity preconditioning in changes of hippocampal neurons and the expression of Gadd45β and DNA-PKcs in the hippocampal region after cerebral ischemia-reperfusion in rats. Method 160 SD rats were divided into control group (n=40), cerebral ischemia reperfusion group (I/R group, n=40), middle intensity exercise preconditioning group (EI 1+I/R group, n=40), high intense exercise preconditioning group (EI 2+I/R group, n=40). Stroke was induced by improved Pulsinelli four blood vessel blocking after exercise preconditioning. Morphological changes of neurons in the hippocampal region of rats were observed by HE staining at 6 h, 1d, 3d and 7d after ischemia in each group. Immunohistochemistry method was used to detect the expression of Gadd45β and DNA-PKcs in hippocampus CA1. The mRNA level of Gadd45β and DNA-PKcs in hippocampal CA1 was detected by Real Time PCR. Results Compared with I/R group, the neuronal cell necrosis of was alleviated in EI 1+I/R group, but more serious in EI 2+I/R group; The expression of Gadd45β and DNA-PKcs were significantly higher in the EI 1+ I/R group, but lower in EI 2+I/R group (PConclusion Moderate intensity exercise preconditioning can improve the survival of neurons after cerebral ischemia-reperfusion injury in rats. However, high-intensity motor preconditioning increased the damage and loss of neurons, and its mechanism may be related to the regulation of the expression of Gadd45β and DNA-PKcs in the hippocampus of cerebral ischemia-reperfusion rats, thus protecting and promoting the function of DNA repair system.},
     year = {2020}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Effect of Different Exercise Intensity Preconditioning on Global Ischemia-Induced Neuronal Death and Expression of Gadd45β and DNA-PKcs in Rats
    AU  - Zhumei Sun
    AU  - Xu Zhao
    AU  - Jianmin Li
    AU  - Yaning Zhao
    AU  - Changxiang Chen
    Y1  - 2020/09/10
    PY  - 2020
    N1  - https://doi.org/10.11648/j.bs.20200603.14
    DO  - 10.11648/j.bs.20200603.14
    T2  - Biomedical Sciences
    JF  - Biomedical Sciences
    JO  - Biomedical Sciences
    SP  - 61
    EP  - 66
    PB  - Science Publishing Group
    SN  - 2575-3932
    UR  - https://doi.org/10.11648/j.bs.20200603.14
    AB  - Background Acute ischemic stroke causes long-term neurological and neurobehavioral dysfunctions. With the development of clinical medicine, the importance of pre-ischemic exercise intervention has been gradually recognized, but its mechanism remains to be further explored. Objective This study investigates the effects of different exercise intensity preconditioning in changes of hippocampal neurons and the expression of Gadd45β and DNA-PKcs in the hippocampal region after cerebral ischemia-reperfusion in rats. Method 160 SD rats were divided into control group (n=40), cerebral ischemia reperfusion group (I/R group, n=40), middle intensity exercise preconditioning group (EI 1+I/R group, n=40), high intense exercise preconditioning group (EI 2+I/R group, n=40). Stroke was induced by improved Pulsinelli four blood vessel blocking after exercise preconditioning. Morphological changes of neurons in the hippocampal region of rats were observed by HE staining at 6 h, 1d, 3d and 7d after ischemia in each group. Immunohistochemistry method was used to detect the expression of Gadd45β and DNA-PKcs in hippocampus CA1. The mRNA level of Gadd45β and DNA-PKcs in hippocampal CA1 was detected by Real Time PCR. Results Compared with I/R group, the neuronal cell necrosis of was alleviated in EI 1+I/R group, but more serious in EI 2+I/R group; The expression of Gadd45β and DNA-PKcs were significantly higher in the EI 1+ I/R group, but lower in EI 2+I/R group (PConclusion Moderate intensity exercise preconditioning can improve the survival of neurons after cerebral ischemia-reperfusion injury in rats. However, high-intensity motor preconditioning increased the damage and loss of neurons, and its mechanism may be related to the regulation of the expression of Gadd45β and DNA-PKcs in the hippocampus of cerebral ischemia-reperfusion rats, thus protecting and promoting the function of DNA repair system.
    VL  - 6
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Department of Clinical Medical, North China University of Science and Technology, Tangshan, China

  • Department of Neurosurgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, China

  • Department of Clinical Medical, North China University of Science and Technology, Tangshan, China

  • Department of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan, China

  • Department of Nursing and Rehabilitation, North China University of Science and Technology, Tangshan, China

  • Sections