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Changes in Genome-Wide DNA Methylation Levels in Different Parts of the Rat Brain in Partial Cerebral Ischemia

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Objectives. To quantify genome-wide DNA methylation in the olfactory bulbs, frontoparietal and occipital areas, and cerebellum in male Wistar rats in normal conditions and in a model of incomplete cerebral ischemia caused by permanent bilateral occlusion of the common carotid arteries. Materials and methods. The study was performed on 23 male Wistar rats, which were divided into sham operation and cerebral ischemia groups. Genome-wide DNA methylation levels at CCGG sites were determined by methyl-sensitive restriction using endonucleases MspI and HpaII, followed by densitometric analysis of electropherograms in ImageJ software. Results and conclusions. Incomplete cerebral ischemia produced 56.3% (95% CI 33.2–76.90) mortality on day 7. Surviving rats of the cerebral ischemia group, as compared with animals of the sham operation group, displayed marked neurological deficit, which was accompanied by changes in the genome-wide DNA methylation level in the nervous tissue of brain structures (p < 0.05). Incomplete cerebral ischemia in male Wistar rats was characterized by interhemispheric asymmetry in the severity and direction of the epigenomic reactions of nervous tissue in both ischemic and non-ischemic areas of the brain. It is likely that these dynamics of changes in the genome-wide DNA methylation status of nervous tissue are responsible for imparting plasticity to neuronal function during ischemic injury.

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References

  1. Stanzione, R., Cotugno, M., Bianchi, F., et al., “Pathogenesis of ischemic stroke: role of epigenetic mechanisms,” Genes (Basel), 11, No. 1, 89 (2020), https://doi.org/https://doi.org/10.3390/genes11010089.

    Article  CAS  Google Scholar 

  2. Zeng, M., Zhen, J., Zheng, X., et al., “The role of DNA methylation in ischemic stroke: A systematic review,” Front. Neurol., 27, No. 11, 566124 (2020), https://doi.org/10.3389/fneur.2020.566124.

  3. Kumar, R., Jain, V., Kushwah, N., et al., “Role of DNA methylation in hypobaric hypoxia-induced neurodegeneration and spatial memory impairment,” Ann. Neurosci., 25, No. 4, 191–200 (2018), https://doi.org/https://doi.org/10.1159/000490368.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shcherbak, N. S., Suchkova, I. O., Patkin, E. L., and Voznyuk, I. A., “DNA methylation in experimental ischemic brain injury,” Zh. Nevrol. Psikhiatr., 122, No. 8, Iss. 2, 32–40 (2022), https://doi.org/10.17116/jnevro202212208232.

  5. Nanduri, J., Semenza, G. L., and Prabhakar, N. R., “Epigenetic changes by DNA methylation in chronic and intermittent hypoxia,” Am. J. Physiol. Lung Cell. Mol. Physiol., 313, 1096–1100 (2017), https://doi.org/https://doi.org/10.1152/ajplung.00325.2017.

    Article  CAS  Google Scholar 

  6. Silva, P. W., Shimon, S. M. M., de Brito, L. M., et al., “Novel insights toward human stroke-related epigenetics: circular RNA and its impact in post stroke processes,” Epigenomics, 12, No. 22, 1957–1968 (2020), https://doi.org/https://doi.org/10.2217/epi-2020-0128.

    Article  PubMed  CAS  Google Scholar 

  7. Rocks, D., Jaric, I., Tesfa, L., et al., “Cell type-specific chromatin accessibility analysis in the mouse and human brain,” Epigenetics, 17, No. 2, 202–219 (2022), https://doi.org/https://doi.org/10.1080/15592294.2021.1896983.

    Article  PubMed  Google Scholar 

  8. Sjöholm, L. K., Ransome, Y., Ekström, T. J., and Karlsson, O., “Evaluation of post-mortem effects on global brain DNA methylation and hydroxymethylation,” Basic Clin. Pharmacol. Toxicol, 122, No. 2, 208–213 (2018), https://doi.org/https://doi.org/10.1111/bcpt.12875.

    Article  PubMed  CAS  Google Scholar 

  9. Tsuchiya, M., Sako, K., Yura, S., and Yonemasu, Y., “Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats,” Exp. Brain Res., 89, 87–92 (1992), https://doi.org/https://doi.org/10.1007/BF00229004.

    Article  PubMed  CAS  Google Scholar 

  10. Farkas, E., Luiten, P. G. M., and Bari, F., “Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases,” Brain Res. Rev., 54, 162–180 (2007), https://doi.org/https://doi.org/10.1016/j.brainresrev.2007.01.003.

    Article  PubMed  CAS  Google Scholar 

  11. Shcherbak, N. S., Vyboldina, T. Yu., Galagudza, M. M., et al., “The impact of early and late ischemic preconditioning of the brain on the extent of damage to hippocampal neurons and the severity of neurological deficit in rats,” Ros. Fiziol. Zh., 98, No. 8, 990–999 (2012).

    CAS  Google Scholar 

  12. Ohno, K., Ito, U., and Inaba, Y., “Regional cerebral blood flow and stroke index after left carotid artery ligation in the conscious gerbil,” Brain Res., 297, 151–157 (1984), https://doi.org/https://doi.org/10.1016/0006-8993 (84)90552-3.

    Article  PubMed  CAS  Google Scholar 

  13. Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, Academic Press, New York (1998).

    Google Scholar 

  14. Schneider, C. A., Rasband, W. S., and Eliceiri, K. W., “NIH Image to ImageJ: 25 years of image analysis,” Nat. Methods, 9, 671–675 (2012), https://doi.org/https://doi.org/10.1038/nmeth.2089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Suchkova, I. O., Dergacheva, N. I., and Pavlinova, L. I., et al., “Quantitative determination of genome-wide DNA methylation using methyl-sensitive restriction and IMAGEJ analysis (MSR-IA),” Mezhdunarod. Nauchn. Issled. Zh., 4, No. 46, Part 5, 41–46 (2016), https://doi.org/10.18454/IRJ.2016.46.096.

  16. Suchkova, I. O., Noniashvili, E. M., Dergacheva, N. I., et al., “The effect of bisphenol A on the level of genome-wide DNA methylation in different parts of the mouse body on day 12 of embryonic development,” Regional. Ekol., 53, No. 3, 96–110 (2018), https://doi.org/10.30694/1026-5600-2018-3-96-110.

  17. Suchkova, I. O., Sasina, L. K., Dergacheva, N. I., et al., “The influence of low dose Bisphenol A on whole genome DNA methylation and chromatin compaction in different human cell lines,” Toxicol. In Vitro, 58, 26–34 (2019), https://doi.org/https://doi.org/10.1016/j.tiv.2019.03.010.

    Article  PubMed  CAS  Google Scholar 

  18. Cerda, S. and Weitzman, S. A., “Influence of oxygen radical injury on DNA methylation,” Mutat. Res., 386, 141–152 (1997), https://doi.org/https://doi.org/10.1016/s1383-5742(96)00050-6.

    Article  PubMed  CAS  Google Scholar 

  19. Lao, V. V., Herring, J. L., Kim, C. H., et al., “Incorporation of 5-chlorocytosine into mammalian DNA results in heritable gene silencing and altered cytosine methylation patterns,” Carcinogenesis, 30, 886–893 (2009), https://doi.org/https://doi.org/10.1093/carcin/bgp060.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Liu, P. K., Hsu, C. Y., Dizdaroglu, M., et al., “Damage, repair, and mutagenesis in nuclear genes after mouse forebrain ischemia-reperfusion,” J. Neurosci., 16, 6795–6806 (1996), https://doi.org/https://doi.org/10.1523/JNEUROSCI.16-21-06795.1996.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Zhao, H., Han, Z., Ji, X., and Luo, Y., “Epigenetic regulation of oxidative stress in ischemic stroke,” Aging Dis., 7, 295 (2016), https://doi.org/10.14336/AD.2015.1009.

  22. Tregub, P. P., Kulikov, V. P., and Malinovskaya, N. A., et al., “HIF-1 – Alternative signals mechanisms for activation and formation of tolerance to hypoxia/ischemia,” Patolog. Fiziol. Eksperim. Ter., 63, No. 4, 115–122 (2019), https://doi.org/10.25557/0031-2991.2019.04.115-122.

  23. Iwai, M., Sato, K., Kamada, H., et al., “Temporal profile of stem cell division, migration, and differentiation from subventricular zone to olfactory bulb after transient forebrain ischemia in gerbils,” J Cereb. Blood Flow Metab., 23, No. 3, 331–341 (2003), https://doi.org/https://doi.org/10.1097/01.WCB.0000050060.57184.E7.

    Article  PubMed  Google Scholar 

  24. Ng, M. R. and Jain, R. K., “Hypoxia-induced DNA hypermethylation: another reason to normalize tumor vessels,” Transl. Cancer Res., 5, No. 7, 34–39 (2016), https://doi.org/10.21037/tcr.2016.12.72.

  25. Cook, N. D., The Brain Code, Methuen, London (1986).

    Google Scholar 

  26. Hartley, I., Elkhoury, F. F., Heon Shin, J., et al., “Long-lasting changes in DNA methylation following short-term hypoxic exposure in primary hippocampal neuronal cultures,” PLoS One, 8, No. 10, 77859 (2013), https://doi.org/https://doi.org/10.1371/journal.pone.0077859.

    Article  CAS  Google Scholar 

  27. Lee, S., Ueno, M., and Yamashita, T., “Axonal remodeling for motor recovery after traumatic brain injury requires downregulation of gamma-aminobutyric acid signaling,” Cell Death Dis., 2, e133 (2011), https://doi.org/https://doi.org/10.1038/cddis.2011.16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Pavlov First St. Petersburg State Medical University, Russian Ministry of Heath, St. Petersburg, Russia

    N. S. Shcherbak & I. A. Voznyuk

  2. Institute of Experimental Medicine, Russian Ministry of Education and Science, St. Petersburg, Russia

    I. O. Suchkova, N. I. Dergacheva & E. L. Patkin

  3. Dzhanelidze Research Institute of Emergency Medicine, Ministry of Health of Russia, St. Petersburg, Russia

    I. A. Voznyuk

Authors
  1. N. S. Shcherbak
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  2. I. O. Suchkova
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  3. N. I. Dergacheva
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  4. E. L. Patkin
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  5. I. A. Voznyuk
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Correspondence to N. S. Shcherbak.

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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 123, No. 3, Iss. 2, pp. 26–32, March, 2023.

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Shcherbak, N.S., Suchkova, I.O., Dergacheva, N.I. et al. Changes in Genome-Wide DNA Methylation Levels in Different Parts of the Rat Brain in Partial Cerebral Ischemia. Neurosci Behav Physi 53, 1360–1365 (2023). https://doi.org/10.1007/s11055-023-01526-1

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  • DOI: https://doi.org/10.1007/s11055-023-01526-1

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