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Inhibiting the H3K9 methylation can preserve the expression of the memory-related protein and ameliorate neurological deficits in vascular dementia
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Fardin Sehati   , Ghorbangol Ashabi , Mina Ranjbaran , Fatemeh Nabavizadeh , Seyed Morteza Karimian , Elham Zahedi |
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Abstract: (271 Views) |
Introduction: Dementia develops as a result of multiple factors including cerebrovascular disease which is called vascular dementia (VD). Histone 3 lysine 9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expression.
Methods and Materials: Common carotid artery occlusion was employed in order to VD induction in male Wistar rats and followed by BIX01294 (H3K9me2 inhibitor) treatment (22.5 µm) intraperitoneally for one month. P-CREB, cfos, brain-derived neurotrophic factor (BDNF), H3K9me2, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were detected at the end of the experimental period. Behavioral tests, hematoxylin and eosin (H&E), Congo red, and TUNEL staining were carried out after treatment. Additionally, Flow cytometry and MTT test were performed in an invitro condition.
Results: Treatment with BIX01294 restored the expression of P-CREB (P <0.05), cfos (P <0.01), BDNF (P <0.01) and lowered the Bax/Bcl2 ratio (P <0.05) by suppressing the H3K9me2 (P <0.001) in the hippocampus of treatment group when compared to the VD group. BIX01294 injection reduced the apoptosis level in TUNEL staining (P <0.05) and raised neural cell count in H&E staining (P <0.01); however, it couldn’t affect amyloid beta accumulation. Furthermore, neurological deficit and anxiety-related behavior significantly reduced in the treatment group against the VD group (P <0.05 for both). BIX01294 consumption also improved spatial and passive avoidance memory (P <0.01 and P <0.05 respectively) against the VD group. The anti-apoptotic impact of BIX01294 was validated by flow cytometry, and finally, the treatment group's cell viability considerably increased as compared to the VD group in the MTT assay (P<0.001).
Conclusion: In summary, long-term treatment with BIX01294 can prevent the progression of neuronal loss after ischemia and reduce the risk of VD by raising the expression of neurotrophic factors and reducing the apoptosis level.
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| Keywords: Vascular dementia, Ischemia, Histone methylation, H3K9 |
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Full-Text [PDF 328 kb]
(51 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/12/16 | Accepted: 2023/08/23 | Published: 2023/08/23
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