HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: A potential role of epigenetics
| Autor: | Mohamed A. Al-Griw, Mansur E. Shmela, Mohamed M. Elhensheri, Emad M. Bennour |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Open Veterinary Journal, Vol 11, Iss 3, Pp 447-457 (2021) |
| Druh dokumentu: | article |
| ISSN: | 2226-4485 2218-6050 |
| DOI: | 10.5455/OVJ.2021.v11.i3.18 |
| Popis: | Background: During development, oligodendrocyte (OL) lineage cells are susceptible to injury, leading to life-long clinical neurodevelopmental deficits, which lack effective treatments. Drugs targeting epigenetic modifications that inhibit histone deacetylases (HDACs) protect from many clinical neurodegenerative disorders. Aim: This study aimed to investigate the therapeutic potential of histone deacetylase 2/3 (HDAC2/3) inhibitor MI192 on white matter (WM) pathology in a model of neonatal rat brain injury. Methods: Wistar rats (8.5-day-old, n=32) were used to generate brain tissues. The tissues were cultured and then randomly divided into 4 groups and treated as following: group I (sham); the tissues were cultured under normoxia, group II (vehicle); DMSO only, group III (injury, INJ); the tissues were exposed to 20 minutes oxygen-glucose deprivation (OGD) insult, and group IV (INJ+MI192); the tissues were subjected to the OGD insult and then treated with the MI192 inhibitor. On culture day 10, the tissues were fixed for biochemical and histological examinations. Results: The results showed that inhibition of HDAC2/3 activity alleviated WM pathology. Specifically, MI192 treatment significantly reduced cell death, minimized apoptosis, and mitigates the loss of the MBP+ OLs and their precursors (NG2+ OPCs). Additionally, MI192 decreased the density of reactive microglia (OX-42+). These findings demonstrate that the inhibition of HDAC2/3 activity post-insult alleviates WM pathology through mechanism(s) including preserving OL lineage cells and suppressing microglial activation. Conclusion: The findings of this study suggest that HDAC2/3 inhibition is a rational strategy to preserve WM or reverse its pathology upon newborn brain injury. |
| Databáze: | Directory of Open Access Journals |
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