HDACi protects against vascular cognitive impairment from CCH injury via induction of BDNF-related AMPA receptor activation

Yao Ching Fang, Jia Yu Hsieh, Amelia Nur Vidyanti, Chih Hao Yang, Jing Shiun Jan, Kang Wei Chang, Chaur Jong Hu, Yong Kwang Tu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

We previously showed a hydroxamic acid-based histone deacetylase inhibitor (HDACi), compound 13, provides neuroprotection against chronic cerebral hypoperfusion (CCH) both in vitro under oxygen-glucose deprivation (OGD) conditions and in vivo under bilateral common carotid artery occlusion (BCCAO) conditions. Intriguingly, the protective effect of this HDACi is via H3K14 or H4K5 acetylation–mediated differential BDNF isoform activation. BDNF is involved in cell proliferation and differentiation in development, synaptic plasticity and in learning and memory related with receptors or synaptic proteins. B6 mice underwent BCCAO and were randomized into 4 groups; a sham without BCCAO (sham), BCCAO mice injected with DMSO (DMSO), mice injected with HDACi-compound 13 (compound 13) and mice injected with suberoylanilide hydroxamic acid (SAHA). The cortex and hippocampus of mice were harvested at 3 months after BCCAO, and levels of BDNF, AMPA receptor and dopamine receptors (D1, D2 and D3) were studied using Western blotting analysis or immunohistochemistry. We found that the AMPA receptor plays a key role in the molecular mechanism of this process by modulating HDAC. This protective effect of HDACi may be through BDNF; therefore, activation of this downstream signalling molecule, for example by AMPA receptors, could be a therapeutic target or intervention applied under CCH conditions.

Original languageEnglish
Pages (from-to)7418-7425
Number of pages8
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number15
DOIs
Publication statusPublished - Aug 2021

Keywords

  • AMPA
  • BDNF
  • CCH
  • HDAC
  • OGD
  • vascular dementia

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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