امروز : چهارشنبه 23 آبان 1397 Rss | صفحه اصلی دانشکده
16 آبان 1395

ارزیابی مدل حیوانی افسردگی و اضطراب در استرس انزوای اجتماعی مزمن در موش کوچک آزمایشگاھی: بررسی نقش نیتریک اکسید

افسردگی و اضطراب در جوامع امروزی به یکی از بیماری‌های گسترده در میان قشرهای مختلف تبدیل شده و بار زیادی به جامعه وارد می‌کند.  با این وجود تا کنون مکانیسم‌های نوروبیولوژیک دقیق مشترک این دو بیماری به طور کامل مشخص نشده است. بر اساس مطالعات اخیر، استرس روانی به‌عنوان عوامل اصلی در بروز افسردگی و اضطراب مطرح شده‌ است. از جمله مدل‌های مورد استفاده در بررسی افسردگی، مدل انزوای اجتماعی (Social Isolation) است که علایم و مکانیسم‌های پاتوفیزیولوژیک مشابه انسان را در حیوان تقلید می‌کند. نیتریک اکسید به عنوان نوعی نورومدولاتور دارای نقش های گسترده ای در فیزیولوژی مغز بوده و نقش آن در بیماری های روان در مطالعات حیوانی نشان داده شده است. با توجه به اثرات ذکر شده و نیاز هرچه بیشتر به مواد القا کننده‌ی اثرات داروهای ضد افسردگی و اضطرابی بر آن شدیم  تا نقش این سیستم را در افسردگی و اضطراب ناشی از استرس انزوای اجتماعی بررسی کنیم. در این راستا، از ایزولاسیون اجتماعی (به مدت 6 هفته در موشهای نوجوان) به عنوان عامل استرسور و از تست‌های رفتاری رایج شناسایی افسردگی در حیوانات شامل تست شنای اجباری (Forced Swimming Test) وSpalsh test جهت بررسی اثر داروها استفاده نمودیم. همچنین برای بررسی تاثیر داروها بر locomotor activity حیوانات، حرکات آنها را در جعبه باز (open field) نظاره کردیم. به منظور ارزیابی اضطراب از تست های رفتاری Hole borad test  و time in central zone بهره بردیم. نتایج نشان داد که استرس مزمن سبب القای بیماری افسردگی و اضطرابی و افزایش سطح نیتریک اکسید مغزی شده است. در قسمت دوم تحقیق به  بررسی اثر ضد افسردگی- ضد اضطرابی داروهای مهارکننده نیتریک اکسید پرداختیم. نتایج به دست آمده نشان داد که مهار آنزیم iNOS سبب القای اثر ضد افسردگی و ضد اضطرابی در موش های استرس دیده شد. در حالی که مهار nNOS فاقد اثر معنا دار بود. همچنین در بررسی غلطت نیتریت در بافت های کورتکس و هیپوکمپ نتایج حاکی از احتمال همخوانی علایم رفتاری و افزایش ناشی از نیتریت کورتکس Prefrontal  داشت. در نهایت، نتایج این تحقیق نشان داد که افزایش سطح نیتریت در کورتکس مغز در پی استرس اجتماعی می تواند عاملی مهم در ایجاد بیماری افسردگی-اضطرابی باشد. امید است در آینده با انجام مطالعات گسترده تر و مطالعات بالینی، بتوان از ترکیبات مهاری iNOS جهت درمان افسردگی  واضطراب استفاده نمود. كليد واژه ها : ایزولاسیون اجتماعی، افسردگی، اضطراب، نیتریک اکسید مشخصات دانشجو: نام: آریا حاج میرزاییان  رشته تحصيلي: پزشکی  مقطع:   دکتری                 گروه آموزشي: پزشکی/فارماکولوژی پست الكترونيك دانشجو: arya.mirzaian@gmail.com اساتيد راهنما و داور:   استاد راهنما:  دکتر احمد رضا دهپور  اساتيد مشاور:-   اساتيد داور: دکتر جزایری زمان دفاع :    روز دوشنبه  تاريخ 10/8/1395  ساعت 11 الی 12 مكان دفاع به آدرس: گروه فارماکولوژی دانشکده ی پزشکی دانشگاه تهران اطلاعات به زبان انگليسي Title:  Evaluation the depressive and anxiety-like behaviors following social isolation stress in mice; possible role of nitrergic system Abstract: Approximately more than 50% patients with depression have the co-occurrence of anxiety, which complicates the treatment of disease. Recently, social isolation stress (SIS) paradigm has been suggested as an animal model to investigate the underlying mechanism involved in depression-anxiety co-occurrence. In this study, applying six weeks of SIS to adolescent mice, we tested whether nitrergic system plays a role in co-occurrence of depression and anxiety. In this study, comparisons between socially and isolated conditioned (SC and IC) animals showed that SIS induces behaviors relevant to depression and anxiety in IC mice and in addition, nitrergic system is involved in mediating the negative outcomes of SIS. Administration of subeffective doses of aminoguanidine (a specific inducible nitric oxide synthase inhibitor or iNOS, 50 mg/kg) and L-NAME (non-specific inhibitor of NOS, 10 mg/kg) significantly reversed the negative effects of SIS on behavioral profile as well as nitrite levels in the cortex of IC mice. Although administration of subeffective dose of 7-nitroindazole (a specific neuronal NOS inhibitor, 25mg/kg) decreased the nitrite levels in the hippocampus, but had no effect on depressant and anxiogenic effects of SIS. Results of this study confirmed that SIS is an appropriate animal model to investigate the potential mechanisms in depression-anxiety cooccurrence. We also showed that nitrergic system is contributed to co-occurring of depression and anxiety in IC mice as an underlying mechanism. Keywords: Social Isolation, Depression, Anxiety, Nitric oxide       فهرست منابع و ماخذ فارسي و لاتين: 1.      Taylor, Daniel J., Kenneth L. Lichstein, H. Heith Durrence, Brant W. Reidel, and Andrew J. Bush. "Epidemiology of insomnia, depression, and anxiety." SLEEP-NEW YORK THEN WESTCHESTER- 28, no. 11 (2005): 1457. 2.      Schoevers, Robert A., et al. "Depression and generalized anxiety disorder: co-occurrence and longitudinal patterns in elderly patients." 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Journal of Psychiatry and Neuroscience, 2004. 29(6): p. 417.       مشخصات مقاله:(در صورتي كه مقاله اي از پايان نامه چاپ يا پذيرش شده است )   عنوان مقاله: Co-occurrence of anxiety and depressive-like behaviors following adolescent social isolation in male mice; possible role of nitrergic system نويسندگان: Amiri, Shayan, Arya Haj-Mirzaian, Maryam Rahimi-Balaei, Ali Razmi, Nastaran Kordjazy, Armin Shirzadian, Shahram Ejtemaei Mehr, Hamed Sianati, and Ahmad Reza Dehpour. نام و شماره مجله : Physiology & behavior 145 (2015): 38-44.


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