اخبار و اعلانات

 آمار

تعداد نشریات286
تعداد نشریات سازمان84
تعداد شماره‌ها2,846
تعداد مقالات32,300
تعداد مشاهده مقاله41,387,099
تعداد دریافت فایل اصل مقاله18,562,174
sehati, Fardin, Ranjbaran, Mina, Karimian, Seyed-Morteza, Nabavizadeh, Fatemeh, Hosseindoost, Saereh, Ashabi, Ghorbangol. (1403). Cerebral inhibition of the H3K9 methylation could ameliorate blood-brain barrier dysfunction and neural damage in vascular dementia. سامانه مدیریت نشریات علمی, 79(5), 989-995. doi: 10.32592/ARI.2024.79.5.989
Fardin sehati; Mina Ranjbaran; Seyed-Morteza Karimian; Fatemeh Nabavizadeh; Saereh Hosseindoost; Ghorbangol Ashabi. "Cerebral inhibition of the H3K9 methylation could ameliorate blood-brain barrier dysfunction and neural damage in vascular dementia". سامانه مدیریت نشریات علمی, 79, 5, 1403, 989-995. doi: 10.32592/ARI.2024.79.5.989
sehati, Fardin, Ranjbaran, Mina, Karimian, Seyed-Morteza, Nabavizadeh, Fatemeh, Hosseindoost, Saereh, Ashabi, Ghorbangol. (1403). 'Cerebral inhibition of the H3K9 methylation could ameliorate blood-brain barrier dysfunction and neural damage in vascular dementia', سامانه مدیریت نشریات علمی, 79(5), pp. 989-995. doi: 10.32592/ARI.2024.79.5.989
sehati, Fardin, Ranjbaran, Mina, Karimian, Seyed-Morteza, Nabavizadeh, Fatemeh, Hosseindoost, Saereh, Ashabi, Ghorbangol. Cerebral inhibition of the H3K9 methylation could ameliorate blood-brain barrier dysfunction and neural damage in vascular dementia. سامانه مدیریت نشریات علمی, 1403; 79(5): 989-995. doi: 10.32592/ARI.2024.79.5.989

Cerebral inhibition of the H3K9 methylation could ameliorate blood-brain barrier dysfunction and neural damage in vascular dementia

Archives of Razi Institute
مقاله 15، دوره 79، شماره 5، آذر و دی 2024، صفحه 989-995    اصل مقاله (504.54 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.32592/ARI.2024.79.5.989
نویسندگان
Fardin sehati1؛ Mina Ranjbaran1؛ Seyed-Morteza Karimian1؛ Fatemeh Nabavizadeh2؛ Saereh Hosseindoost3؛ Ghorbangol Ashabi* 1
1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
31Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
چکیده
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.
کلیدواژه‌ها
H3K9؛ Brain edema؛ Blood-brain barrier؛ Vascular dementia؛ Cerebral ischemia
عنوان مقاله [English]
مهار داخل مغزی متیلاسیون H3K9 اختلال عملکرد سد خونی مغزی را بهبود بخشیده و آسیب نورونی را در دمانس عروقی کاهش می دهد
چکیده [English]
سابقه و هدف: دمانس عروقی (VD) دومین عامل اختلال شناختی در جهان است که منجر به کاهش پیش رونده توانایی تفکر و یادآوری در بیمار می‌گردد. مطالعات انجام شده در این زمینه نشان داده‌اند آنزیم G9a/GLP با افزایش دی‌متیلاسیون لیزین شماره 9 در هیستون شماره 3 (H3K9me2) نقش کلیدی در بروز VD ایفا می‌کند.
مواد و روش‌ها: در مطالعه حاضر اثر مهارکننده G9a/GLP، با نام تجاری BIX01294 بر روی VD با استفاده از مدل انسداد دائمی شریان-های کاروتید مشترک مورد بررسی قرار گرفت. BIX01294 (22.5µg.kg-1 ) به صورت داخل صفاقی سه بار در هفته و به مدت یک ماه تجویز شد. رنگ آمیزی نیسل، تست آبی ایوانس و محتوای آب مغزی تعیین شده و سطح فاکتورهای آپوپتوزی با استفاده از تکنیک وسترن بلات در ناحیه هیپوکامپ مورد بررسی قرار گرفت.
یافته‌ها: استفاده از BIX01294 باعث افزایش مقاومت سد خونی مغزی (P<0.05) و متعاقبا کاهش محتوای آب مغزی در مقایسه با گروه VD شد (P <0.05 برای هر دو). تزریق BIX01294 میزان مرگ نورونی در ناحیه هیپوکامپ را در گروه درمان نسبت به گروه VD بهبود بخشید (P<0.05). از سوی دیگر، نسبت Bax/Bcl2 به طور قابل توجهی در گروه درمان نسبت به گروه VD کاهش یافت (P <0.0001).
نتیجه‌گیری: مطالعه‌ی حاضر نشان داد مهار متیلاسیون H3K9 توسط BIX01294 از طریق کاهش ادم مغزی و سطح آپوپتوز از آسیب نورونی متعاقب ایسکمی مغزی جلوگیری کرده و می‌تواند یک هدف جدید برای کنترل VD باشد.
کلیدواژه‌ها [English]
H3K9, ادم مغزی, سد خونی مغزی, زوال عقل عروقی, ایسکمی مغزی
مراجع
  1. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):1–18.
  2. Yang Y, Zhao X, Zhu Z, Zhang L. Vascular dementia: A microglia’s perspective. Ageing Res Rev. 2022;101734.
  3. Karlić R, Chung HR, Lasserre J, Vlahoviček K, Vingron M. Histone modification levels are predictive for gene expression. Proc Natl Acad Sci. 2010;107(7):2926–31.
  4. Dong X, Weng Z. The correlation between histone modifications and gene expression. Epigenomics. 2013;5(2):113–6.
  5. Afonso J, Shim WJ, Boden M, Fortes MRS, da Silva Diniz WJ, de Lima AO, et al. Repressive epigenetic mechanisms, such as the H3K27me3 histone modification, were predicted to affect muscle gene expression and its mineral content in Nelore cattle. Biochem Biophys Reports. 2023;33:101420.
  6. Jhelum P, C Karisetty B, Kumar A, Chakravarty S. Implications of epigenetic mechanisms and their targets in cerebral ischemia models. Curr Neuropharmacol. 2017;15(6):815–30.
  7. Chakravarty S, Jhelum P, Bhat UA, Rajan WD, Maitra S, Pathak SS, et al. Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication. Biochim Biophys Acta (BBA)-Molecular Basis Dis. 2017;1863(1):152–64.
  8. Schweizer S, Harms C, Lerch H, Flynn J, Hecht J, Yildirim F, et al. Inhibition of histone methyltransferases SUV39H1 and G9a leads to neuroprotection in an in vitro model of cerebral ischemia. J Cereb Blood Flow Metab. 2015;35(10):1640–7.
  9. Wilson C, Giono LE, Rozes-Salvador V, Fiszbein A, Kornblihtt AR, Caceres A. The histone methyltransferase G9a controls axon growth by targeting the RhoA signaling pathway. Cell Rep. 2020;31(6).
  10. Nativio R, Lan Y, Donahue G, Sidoli S, Berson A, Srinivasan AR, et al. An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease. Nat Genet. 2020;52(10):1024–35.
  11. Lee MY, Lee J, Hyeon SJ, Cho H, Hwang YJ, Shin J, et al. Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer’s disease. Aging Cell. 2020;19(6):e13153.
  12. Gupta-Agarwal S, Franklin A V., DeRamus T, Wheelock M, Davis RL, McMahon LL, et al. G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation. J Neurosci. 2012;32(16):5440–53.
  13. Zarrindast MR, Nasehi M, Piri M, Bina P. Anxiety-like behavior induced by histaminergic agents can be prevented by cannabinoidergic WIN55, 212-2 injected into the dorsal hippocampus in mice. Pharmacol Biochem Behav. 2010;94(3):387–96.
  14. Ooigawa H, Nawashiro H, Fukui S, Otani N, Osumi A, Toyooka T, et al. The fate of Nissl-stained dark neurons following traumatic brain injury in rats: difference between neocortex and hippocampus regarding survival rate. Acta Neuropathol. 2006;112:471–81.
  15. Farbood Y, Sarkaki A, Khalaj L, Khodagholi F, Badavi M, Ashabi G. Targeting Adenosine Monophosphate-Activated Protein Kinase by Metformin Adjusts Post-Ischemic Hyperemia and Extracellular Neuronal Discharge in Transient Global Cerebral Ischemia. Microcirculation. 2015;22(7):534–41.
  16. Soltani N, Soltani Z, Khaksari M, Ebrahimi G, Hajmohammmadi M, Iranpour M. The changes of brain edema and neurological outcome, and the probable mechanisms in diffuse traumatic brain injury induced in rats with the history of exercise. Cell Mol Neurobiol. 2020;40(4):555–67.
  17. Cacabelos R, Teijido O. Epigenetic drug discovery for Alzheimer’s disease. Epigenetics aging Longev. 2018;453–95.
  18. Shan W, Wu Y, Han X, Chen Q, Wu J. The mechanism of sevoflurane post-treatment alleviating hypoxic-ischemic encephalopathy by affecting histone methyltransferase G9a in rats. Bioengineered. 2021;12(2):9790–805.
  19. Sharifulina S, Dzreyan V, Guzenko V, Demyanenko S. Histone methyltransferases SUV39H1 and G9a and DNA methyltransferase DNMT1 in penumbra neurons and astrocytes after photothrombotic stroke. Int J Mol Sci. 2021;22(22):12483.
  20. Sadli N, Ackland ML, De Mel D, Sinclair AJ, Suphioglu C. Effects of zinc and DHA on the epigenetic regulation of human neuronal cells. Cell Physiol Biochem. 2012;29(1–2):87–98.
  21. Shi R, Zheng C bo, Wang H, Rao Q, Du T, Bai C, et al. Gastrodin alleviates vascular dementia in a 2-VO-vascular dementia rat model by altering amyloid and tau levels. Pharmacology. 2020;105(7–8):386–96.
  22. Padurariu M, Ciobica A, Lefter R, Serban IL, Stefanescu C, Chirita R. The oxidative stress hypothesis in Alzheimer’s disease. Psychiatr Danub. 2013;25(4):401–9.
  23. Hudson LC, Bragg DC, Tompkins MB, Meeker RB. Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells. Brain Res. 2005;1058(1–2):148–60.
  24. Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015;85(2):296–302.
  25. Erickson MA, Banks WA. Age-associated changes in the immune system and blood–brain barrier functions. Int J Mol Sci. 2019;20(7):1632.
  26. Park MJ, Sohrabji F. The histone deacetylase inhibitor, sodium butyrate, exhibits neuroprotective effects for ischemic stroke in middle-aged female rats. J Neuroinflammation. 2016;13:1–14.
  27. Wang Z, Leng Y, Tsai LK, Leeds P, Chuang DM. Valproic acid attenuates blood–brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. J Cereb Blood Flow Metab. 2011;31(1):52–7.
  28. Su L, Liang D, Kuang SY, Dong Q, Han X, Wang Z. Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury. Neural Regen Res. 2020;15(2):277.
  29. Imakita N, Kitabatake M, Ouji-Sageshima N, Hara A, Morita-Takemura S, Kasahara K, et al. Abrogated Caveolin-1 expression via histone modification enzyme Setdb2 regulates brain edema in a mouse model of influenza-associated encephalopathy. Sci Rep. 2019;9(1):284.
آمار
تعداد مشاهده مقاله: 200
تعداد دریافت فایل اصل مقاله: 130


counter
سامانه مدیریت نشریات علمی. قدرت گرفته از سیناوب