Document Type : Original Articles
Authors
1
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
3
1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
10.22092/ari.2024.364424.2978
Abstract
Dementia is a broad category of brain diseases denoting various brain diseases with degenerative or vascular components that cause a long-term and often gradual decrease in the ability to think and remember severe enough to affect daily functioning. Literature has indicated that the G9a/GLP enzyme, through upregulating histone 3 lysine 9 dimethylation (H3K9me2), is a major effector in VD. In such a way that the increase of H3K9 methylation by G9a/GLP during vascular dementia leads to inhibiting the expression of neuroprotective proteins and also reduces the expression of proteins that play a crucial role in the blood brain barrier function.
Using a model of permanent common carotid arteries (CCA) occlusion, we investigated the impact of a G9a/GLP inhibitor (BIX01294) on VD. After occlusion of the CCA, BIX01294 (22.5µg.kg-1 ) was given intraperitoneally three times a week for a month. Nissl staining, Evans blue, and brain water content were assessed and western blot analysis was used to evaluate the hippocampal levels of Bax and Bcl2.
Using BIX01294 enhanced blood-brain barrier stability (P <0.05) and subsequently reduced brain edema in comparison to the VD group (P <0.05 for both). Neural injury in the CA1 area of the treatment group decreased by BIX01294 injection when compared to the VD group (P<0.05). On the other hand, the Bax/Bcl2 ratio considerably decreased in the treatment group (P <0.0001). To summarize, our research shows that inhibiting H3K9 methylation can prevent the development of vascular dementia by reducing the level of cerebral edema and neural apoptosis in the hippocampus area after ischemic stroke.
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