E-ISSN 2218-6050 | ISSN 2226-4485
 

Original Article


HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics

Mohamed A Al-Griw, Mansur E Shmela, Mohamed M Elhensheri, Emad M Bennour.

Abstract
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 the 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. At 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 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.

Key words: brain injury, epigenetics, MI192, microglia, oligodendrocytes.


 
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How to Cite this Article
Pubmed Style

Al-Griw MA, Shmela ME, Elhensheri MM, Bennour EM, . HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. Open Vet J. 2021; 11(3): 447-457. doi:10.5455/OVJ.2021.v11.i3.18


Web Style

Al-Griw MA, Shmela ME, Elhensheri MM, Bennour EM, . HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. https://www.openveterinaryjournal.com/?mno=76556 [Access: February 05, 2023]. doi:10.5455/OVJ.2021.v11.i3.18


AMA (American Medical Association) Style

Al-Griw MA, Shmela ME, Elhensheri MM, Bennour EM, . HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. Open Vet J. 2021; 11(3): 447-457. doi:10.5455/OVJ.2021.v11.i3.18



Vancouver/ICMJE Style

Al-Griw MA, Shmela ME, Elhensheri MM, Bennour EM, . HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. Open Vet J. (2021), [cited February 05, 2023]; 11(3): 447-457. doi:10.5455/OVJ.2021.v11.i3.18



Harvard Style

Al-Griw, M. A., Shmela, M. E., Elhensheri, M. M., Bennour, E. M. & (2021) HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. Open Vet J, 11 (3), 447-457. doi:10.5455/OVJ.2021.v11.i3.18



Turabian Style

Al-Griw, Mohamed A, Mansur E Shmela, Mohamed M Elhensheri, Emad M Bennour, and . 2021. HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. Open Veterinary Journal, 11 (3), 447-457. doi:10.5455/OVJ.2021.v11.i3.18



Chicago Style

Al-Griw, Mohamed A, Mansur E Shmela, Mohamed M Elhensheri, Emad M Bennour, and . "HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics." Open Veterinary Journal 11 (2021), 447-457. doi:10.5455/OVJ.2021.v11.i3.18



MLA (The Modern Language Association) Style

Al-Griw, Mohamed A, Mansur E Shmela, Mohamed M Elhensheri, Emad M Bennour, and . "HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics." Open Veterinary Journal 11.3 (2021), 447-457. Print. doi:10.5455/OVJ.2021.v11.i3.18



APA (American Psychological Association) Style

Al-Griw, M. A., Shmela, M. E., Elhensheri, M. M., Bennour, E. M. & (2021) HDAC2/3 inhibitor MI192 mitigates oligodendrocyte loss and reduces microglial activation upon injury: a potential role of epigenetics. Open Veterinary Journal, 11 (3), 447-457. doi:10.5455/OVJ.2021.v11.i3.18