بررسی نقش استرس شبکه اندوپلاسمی در پیشرفت پارکینسونیسم القاء شده با سم 6- هیدروکسی دپامین در موش بزرگ ازمایشگاهی

نوع مقاله : مقاله پژوهشی

نویسندگان

مرکز تحقیقات سلولی و ملکولی، پژوهشکده جلوگیری از بیماری های غیر واگیر، دانشگاه علوم پزشکی قزوین، قزوین، ایران

چکیده

هدف: در این مطالعه  با بررسی بیان دو پروتئین شاخص استرس شبکه آندوپلاسمی (ER), GRP78 و CHOP در استریاتوم و جسم سیاه (SN) در مدل حیوانی  6- هیدروکسی دپامین (6-OHDA) بیماری پارکینسون نقش این استرس در پیشرفت این بیماری بررسی شد.
مواد و روش ها: سم 6-OHDA به ناحیه دسته مغزی جلویی میانی تزریق شد. آزمون های رفتاری در هفته های دوم، چهارم، ششم و هشتم پس از سم انجام شد. در هفته هشتم مغز برخی موش ها پرفیوز و بررسی های ایمونوهیستوشیمی برای ارزیابی بقاء نورون های دپامینرژیک در جسم سیاه و میزان بیان GRP78 وCHOP در استریاتوم صورت گرفت. مغز دیگر موش ها تازه دراورده شد و بیان GRP78 و CHOP در SN بوسیله وسترن بلاتینگ بررسی شد.
نتایج: شدت علائم رفتاری در موش های دریافت کننده سم بتدریج افزایش یافت و در هفته هشتم به حداکثر رسید. ردیابی ایمونو هیستوشیمی در SN نشان داد که بیش از 80 درصد از نورون‌های دپامینرژیک جسم سیاه در موش های دریافت کننده سم تخریب شدند. همچنین با وجود آنکه درگروه کنترل تنها 5% از سلول ها در استریاتوم پروتئین های GRP78 و CHOP را بیان کردند در گروه دریافت کننده سم میزان بیان این پروتئین ها 42% بود. در جسم سیاه گروه سم نیز بیان این پروتئین ها نزدیک به 400% افزایش یافت.
نتیجه‌گیری: استرس ER در پیشرفت پارکینسونیسم القاء شده با 6-OHDA در موش بزرگ ازمایشگاهی نقش دارد که دلالت می کند این استرس ممکن است نقشی در پیشرفت بیماری پارکینسون در انسان داشته باشد.  

کلیدواژه‌ها

عنوان مقاله [English]

Evaluation of the role of endoplasmic reticulum stress in the progress of 6-hydroxydopamine-induced Parkinsonism in rat

نویسندگان [English]

  • Azita Minaei
  • Hashem Haghdoost-Yazdi
  • Mohammad Reza Sarookhani
Cellular and Molecular Research Center, Research Institute for Prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran
چکیده [English]

Objective: In this study, using evaluation of the expression of two specific proteins of endoplasmic reticulum (ER) stress, GRP78 and CHOP in the striatum and substantia nigra (SN) in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson’s disease (PD), the role of this stress was evaluated in the progress of Parkinson's disease (PD). 
Materials and Methods: 6-OHDA was injected into medial forebrain bundle. Behavioral tests were carried out in the second, forth, sixth and eighth weeks after the toxin. In the eighth week, the brain of some rats was perfused and immunohistochemical (IHC) assessments were performed to evaluate the survival of dopaminergic neurons in SN and also the expression of GRP78 and CHOP in striatum. The brain of other rats was freshly removed and the expression of GRP78 and CHOP in SN was evaluated using western blotting.
Results: The severity of behavioral symptoms increased progressively in 6-OHDA- treated rats and reached to maximum in the eighth week. IHC assessments revealed that more than 80% of dopaminergic neurons in SN were lost in these rats. These assessments also showed that only 5% of the cells in striatum of control rats expressed GRP78 and CHOP. On the other hand, about 42% of these cells in 6-OHDA- treated rats expressed these proteins. Furthermore, expression of GRP78 and CHOP in SN of 6-OHDA- treated rats increased 400% as compared to control rats.
Conclusion: ER stress involves in progress of 6-OHDA-induced parkinsonism in rat indicating this stress may have a role in progress of PD in human beings.

کلیدواژه‌ها [English]

  • Parkinson’s disease
  • 6-hydroxydopamine
  • GRP78
  • CHOP
  • Striatum
  • Substantia nigra
  • Rat

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