17b-استرادیول دمیلیناسیون را از طریق تقویت قطبیت میکروگلیا M2 و تنظیم NLRP3 Inflammasome در موش های تغذیه شده با کوپریزون کاهش می دهد

آریانپور, رویا and زیبارا, کاظم and پاسبخش, پریچهر and جامعی, سید بهنام الدین and نامجو, زینب and قنبری, امیر and محمودی, رضا and امانی, شورا and راگردی کاشانی, ایرج (1400) 17b-استرادیول دمیلیناسیون را از طریق تقویت قطبیت میکروگلیا M2 و تنظیم NLRP3 Inflammasome در موش های تغذیه شده با کوپریزون کاهش می دهد. NEUROSCIENCE ــ 463 . pp. 116-127. شاپا 0306-4522

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17b-Estradiol Reduces Demyelination in Cuprizone-fed Mice by Promoting M2 Microglia Polarity and Regulating NLRP3 Inflammasome

English Abstract

produces a beneficial role in animal models of multiple sclerosis (MS). The effect of 17pestradiol therapy on microglia polarization and neuroinflammation in the corpus callosum of the cuprizoneinduced demyelination model has not been elucidated. In this study, mice were given 0.2% cuprizone (CPZ) for 5 weeks to induce demyelination during which they received 50 ng of 17p-estradiol (EST), injected subcutaneously in the neck region, twice weekly. Data revealed that treatment with 17p-estradiol therapy (CPZ+EST) improved neurological behavioral deficits, displayed by a significant reduction in escape latencies, in comparison to untreated CPZ mice. Also, administration of 17p-estradiol caused a decrease in demyelination levels and axonal injury, as demonstrated by staining with Luxol fast blue, immunofluorescence to myelin basic protein, and transmission electron microscopy analysis. In addition, at the transcriptional level in the brain, mice treated with 17pestradiol (CPZ+EST) showed a decrease in the levels of M1-assosicted microglia markers (CD86, iNOS and MHCII) whereas M2-associated genes (Arg-1, CD206 and Trem-2) were increased, compared to CPZ mice. Moreover, administration of 17p-estradiol resulted in a significant reduction (-3-fold) in transcript levels of NLRP3 inflammasome and its downstream product IL-18, compared to controls. In summary, this study demonstrated for the first time that exogenous 17p-estradiol therapy robustly leads to the reduction of M1 phenotype, stimulation of polarized M2 microglia, and repression of NLRP3 inflammasome in the corpus callosum of CPZ demyelination model of MS. The positive effects of 17p-estradiol on microglia and inflammasome seems to facilitate and accelerate the remyelination process. ? 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :رویا آریانپور
نویسنده مسئول :کاظم زیبارا
نویسنده :پریچهر پاسبخش
نویسنده :سید بهنام الدین جامعی
نویسنده :زینب نامجو
نویسنده :امیر قنبری
نویسنده :رضا محمودی
نویسنده :شورا امانی
نویسنده مسئول :ایرج راگردی کاشانی
Additional Information:IF: 3.59 Indexed in: ISI, Scopus, PubMed/Medline, Embase
Uncontrolled Keywords:17بتا استرادیول، میکروگلی، التهاب عصبی، اینفلامازوم، مالتیپل اسکلروزیس
کلیدواژه ها (انگلیسی):17b-estradiol, microglia, neuroinflammation, inflammasome, multiple sclerosis
Subjects:QV pharmacology
WL Nervous system
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of Anatomy
ID Code:14833
Deposited By: Dr Zeinab Namjoo
Deposited On:24 Dec 1400 08:10
Last Modified:24 Dec 1400 08:10

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