HDACi protects against vascular cognitive impairment from CCH injury via induction of BDNF‐related AMPA receptor activation
| Autor: | Chih-Hao Yang, Yao-Ching Fang, Yong Kwang Tu, Jing-Shiun Jan, Chaur-Jong Hu, Amelia Nur Vidyanti, Jia-Yu Hsieh, Kang-Wei Chang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Hippocampus Arterial Occlusive Diseases AMPA receptor Pharmacology Neuroprotection Mice In vivo HDAC AMPA medicine Animals Receptors AMPA CCH Receptor Cerebral Cortex Chemistry Brain-Derived Neurotrophic Factor Dementia Vascular Histone deacetylase inhibitor OGD vascular dementia Cell Biology Original Articles Histone Deacetylase Inhibitors Mice Inbred C57BL BDNF Carotid Arteries Neuroprotective Agents nervous system Dopamine receptor Synaptic plasticity Molecular Medicine Original Article |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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