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Inhibition of histone deacetylase 3 by MiR-494 alleviates neuronal loss and improves neurological recovery in experimental stroke.
- Source :
- Journal of Cerebral Blood Flow & Metabolism; Dec2019, Vol. 39 Issue 12, p2392-2405, 14p
- Publication Year :
- 2019
-
Abstract
- HDAC3 is an essential negative regulator of neuronal plasticity and memory formation. Although a chemical inhibitor has been invented, little is known about its endogenous modulators. We explored whether miR-494 affects HDAC3-mediated neuronal injury following acute ischemic stroke. A substantial increase in plasma miR-494 was detected in AIS patients and was positively associated with the mRS at one year after symptom onset. The miR-494 levels were transiently increased in the infarcted brain tissue of mice. In contrast, miR-494 levels were reduced in neurons but increased in the medium after OGD. Intracerebroventricular injection of miR-494 agomir reduced neuronal apoptosis and infarct volume at the acute stage of MCAO, promoted axonal plasticity and long-term outcomes at the recovery stage, suppressed neuronal ataxin-3 and HDAC3 expression and increased acetyl-H3K9 levels in the ipsilateral hemisphere. In vitro studies confirmed that miR-494 posttranslationally inhibited HDAC3 in neurons and prevented OGD-induced neuronal axonal injury. The HDAC3 inhibitor increased acetyl-H3K9 levels and reversed miR-494 antagomir-aggravated acute cerebral ischemic injury, as well as brain atrophy and long-term functional recovery. These results suggest that miR-494 may serve as a predictive biomarker of functional outcomes in AIS patients and a potential therapeutic target for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0271678X
- Volume :
- 39
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 140065195
- Full Text :
- https://doi.org/10.1177/0271678X19875201