Abstract Histone modifications, as epigenetic regulators, play a crucial role in the pathogenesis and progression of vascular cognitive impairment (VCI). It remains unclear whether electroacupuncture (EA), a clinically effective therapy, can ameliorate VCI through mechanisms involving histone modifications. A VCI rat model was established through chronic cerebral hypoperfusion induced by two‐vessel occlusion surgery. Acetylproteomics and chromatin immunoprecipitation sequencing (ChIP‐seq) screened histone acetylation sites and target genes affected by EA, and these were verified by western blot and real time fluorescence quantitative PCR. Recombinant adeno‐associated virus (rAAV) mediated SIRT7 knockdown promotes hippocampal H3K18 acetylation (H3K18ac). Cognitive function and synaptic plasticity were assessed via Barnes maze, Morris water maze, Golgi staining and patch‐clamp electrophysiology. Acetylproteomics identified histone H3 lysine 18 as a key acetylation site targeted by EA in VCI. ChIP‐seq further screened Ubp1 and Galc promoter as downstream target genes responsive to EA‐mediated regulation of H3K18ac. SIRT7 was promoted by EA, and rAAV‐mediated inhibition of SIRT7 successfully induced hippocampal H3K18 hyperacetylation in VCI rats, increased H3K18ac enrichment at the Ubp1 promoter, and consequently inhibited EA‐induced improvements in dendritic spine density, long‐term potentiation, and cognition. This study demonstrates that EA enhances synaptic plasticity and ameliorates cognitive deficits in VCI rats by upregulating SIRT7, which suppresses H3K18ac at the promoter of its target gene Ubp1 , leading to reduced expression. Concurrently, EA upregulates H3K18ac at the Galc promoter, enhancing GALC expression, although the specific regulatory enzyme involved has yet to be determined.
Wang et al. (Sun,) studied this question.
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