Expression patterns of histone deacetylases in experimental stroke and potential targets for neuroprotection

Authors

  • Yan-Ting Chen,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
    2. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
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  • Xue-Feng Zang,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
    2. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
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  • Jie Pan,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
    2. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
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  • Xiao-Lei Zhu,

    1. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    2. Department of Neurology, Affiliated Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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  • Fei Chen,

    1. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    2. Department of Neurology, Affiliated Drum Tower Hospital, Nanjing Medical University, Nanjing, China
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  • Zhi-Bin Chen,

    1. Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
    2. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
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  • Yun Xu

    Corresponding author
    1. Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    2. Department of Neurology, Affiliated Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
    3. Department of Neurology, Affiliated Drum Tower Hospital, Nanjing Medical University, Nanjing, China
    • Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Correspondence: Yun Xu, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 ZhongShan Road, Nanjing City, Jiangsu Province 210008, China.

Email: xuyun20042001@yahoo.com.cn

Summary

  1. Histone deacetylase (HDAC) inhibitors exert neuroprotection in both cellular and animal models of ischaemic stroke. However, which HDAC isoform (or isoforms) mediates this beneficial effect has not yet been determined.
  2. In the present study, gene levels of the HDAC isoforms were determined in the mouse cortex using reverse transcription–polymerase chain reaction (RT-PCR), whereas changes in the expression of individual zinc-dependent HDAC family members were evaluated by western blotting, 3, 12, 24 and 48 h after cerebral ischaemia induced by transient middle cerebral artery occlusion in male Kunming mice.
  3. The HDAC isoforms HDAC1–11 were all expressed in the mouse cortex and differentially affected by cerebral ischaemia. Notably, there was a substantial increase in HDAC3, HDAC6 and HDAC11 expression during the early phases of experimental stroke, indicating their contribution to stroke pathogenesis. Furthermore, induction of HDAC3 and HDAC6 in cortical neurons by ischaemic stroke was confirmed in vivo and in vitro using double-labelled immunostaining and RT-PCR, respectively. Therefore, small hairpin (sh) RNAs were used to selectively knock down HDAC3 or HDAC6. This knockdown appreciably promoted the survival of cortical neurons subjected to oxygen and glucose deprivation.
  4. The findings of the present study demonstrate the expression patterns of HDAC isoforms during experimental ischaemic stroke. Furthermore, HDAC3 and HDAC6 were identified as potential mediators in the neurotoxicity of ischaemic stroke, suggesting that specific therapeutic approaches may be considered according to HDAC subtype.

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