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Epigenetic Signature of Chronic Cerebral Hypoperfusion and Beneficial Effects of S-adenosylmethionine in Rats

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Abstract

Chronic cerebral hypoperfusion is associated with cognitive decline in aging and age-related neurodegenerative disease. Epigenetic mechanisms are involved in the maintenance of long-term hypoxia-adapted cellular phenotypes. In the present study, the epigenetic signatures such as DNA methylation and histone acetylation, as well as S-adenosylmethionine (SAM) cycle using chronic cerebral hypoperfusion rat model were explored. Chronic cerebral hypoxia-induced global DNA hypermethylation associated with the increase of DNA methyltransferase (DNMT) 3A as well as alteration of SAM cycle. Meanwhile, an enhanced level of global histone H4 acetylation accompanied with the upregulation of histone acetyltransferase, p300/CREB-binding protein (CBP), and the downregulation of histone deacetylases (HDACs), was also observed. SAM could improve spatial capacity through the upregulation of acetylcholine and brain-derived neurotrophic factor (BDNF) rather than alteration of DNA methylation levels. In conclusion, we have demonstrated a genome-wide adjustment of DNA methylation and histone acetylation under chronic cerebral hypoxic conditions in a rat’s brain. These epigenetic signatures may represent an additional mechanism to promote and maintain a hypoxic-adapted cellular responds with a potential role in memory deficits.

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Acknowledgments

This work was supported by National Natural Science Foundation (Nos. 81070926 and 81271310) and China 973 Preprogram (2011CB512109).

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The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, People’s Republic of China

    Xiangmei Wu, Jing Sun, Xiaowen Zhang, Xiaona Li, Zichen Liu, Qinglin Yang & Liang Li

  2. Department of Pathology, Capital Medical University, 10 Xi Tou Tiao, You An Men Street, Beijing, 100069, People’s Republic of China

    Liang Li

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  1. Xiangmei Wu
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Correspondence to Liang Li.

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Wu, X., Sun, J., Zhang, X. et al. Epigenetic Signature of Chronic Cerebral Hypoperfusion and Beneficial Effects of S-adenosylmethionine in Rats. Mol Neurobiol 50, 839–851 (2014). https://doi.org/10.1007/s12035-014-8698-5

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  • DOI: https://doi.org/10.1007/s12035-014-8698-5

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