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Myricitrin ameliorates cognitive deficits in MCAO cerebral stroke rats via histone acetylation-induced alterations of brain-derived neurotrophic factor

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Abstract

The present study screened the effect of Myricitrin on cognitive deficits post-cerebral ischemic stroke and the involved mechanism. The rats were submitted to middle cerebral artery occlusion (MCAO) and were treated with sodium butyrate or Myricitrin (15 and 30 mg/kg) for 28 days. The spatial memory was studied by Morris water maze (MWM). After 4 weeks, the rats were euthanized and hippocampus region was utilized for neurochemical and biochemical changes. The extent of histone acetylation was studied by ELISA. Protein levels were analyzed by Western blot analysis. The mRNA levels were analyzed by polymerase chain reaction (PCR). In silico bioinformatics docking studies were done for target confirmation of Myricitrin. The treatment of Myricitrin showed improved memory in MWM compared to rats treated with vehicle, and the effects of Myricitrin were similar to sodium butyrate-treated rats. At a dose of 30 mg/kg Myricitrin, the histone deacetylase content was decreased, the expression levels of BDNF were increased, the levels of acetylated H3 and H4 along with Syn-I in the hippocampus region were over-expressed compared to control vehicle-treated rats. However, at low dose, i.e., 15 mg/kg Myricitrin failed to show alterations in biochemical as well as neurochemical markers. Docking studies suggested the BDNF and Sun-I as potential target proteins of Myricitrin. The cognitive ameliorating effect of Myricitrin post-cerebral ischemia stroke can be attributed to increased expression of BDNF and Syn-I and modulation of histone acetylation.

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Acknowledgements

The authors are thankful to Basic Medical School of Jining Medical University China and also to the funding agencies.

Funding

This study was supported by The National Natural Science Foundation of China (No. 81703490), NSFC cultivation project of Jining Medical University (No. JYP2018KJ06), and The Support Foundation of Jining Medical College (No. JY2017KJ018).

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Authors and Affiliations

  1. Department of Histology and Embryology, Basic Medical School of Jining Medical University, Jining, 272001, Shandong, China

    Yang Gao, Xiaojin Li, Yan Guo & Haiyan Yin

  2. Department of Physiology, Basic Medical School of Jining Medical University, Jining, 272001, Shandong, China

    Bailiu Ya

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  1. Yang Gao
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  2. Bailiu Ya
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  3. Xiaojin Li
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  4. Yan Guo
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Correspondence to Yang Gao.

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Gao, Y., Ya, B., Li, X. et al. Myricitrin ameliorates cognitive deficits in MCAO cerebral stroke rats via histone acetylation-induced alterations of brain-derived neurotrophic factor. Mol Cell Biochem 476, 609–617 (2021). https://doi.org/10.1007/s11010-020-03930-4

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