اثر درمانی متفورمین بر مرگ سلولی نکروتیک سلول های هیپوکمپ و بهبود اختلال حافظه فضایی در موش صحرایی نر مدل سندرم جنین الکلی

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه زیست شناسی ، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران

2 مرکز تحقیقات اعتیاد، دانشگاه علوم پزشکی شاهرود، شاهرود، ایران

چکیده

مواجهه با الکل در دوران جنینی سبب طیف گسترده­ای از آثار فیزیولوژیکی و رفتاری طولانی مدت می­شود که در مجموع اختلال سندرم جنین الکلی (FASD) نامیده می­شود.اختلالات عصبی ناشی از سوء مصرف الکل در کودکان با آپوپتوز در چندین منطقه از مغز مانند هیپوکامپ که به دنبال فعال شدن آبشار اکسیداتیو- التهابی و سطح بالای دژنراسیون عصبی رخ می­دهد مرتبط است. مطالعات نشان دادند که متفورمین (1،1- دی­متیل هیدروکلراید) که به عنوان داروی خط اول برای درمان دیابت نوع 2 استفاده می­شود می­تواند به سرعت از سد خونی مغزی عبور کرده و آثار نوروپروتکتیو آن در چندین بیماری سیستم عصبی مورد تأیید قرار گرفته است. این پژوهش با هدف ارزیابی فعالیت­های محافظتی متفورمین بر روی اختلالات حافظه و نکروز سلول­های عصبی در هیپوکامپ موش صحرایی با قرار گرفتن در معرض الکل پس از تولد انجام شد.نوزادان نر موش صحرایی 5.27 گرم در کیلوگرم اتانول محلول در 8.27 میلی­لیتر بر کیلوگرم شیر خشک را از طریق گاواژ در روزهای 10-2 بعد از تولد دریافت کردند .نوزادان همچنین 20 و 40 میلی­گرم بر کیلوگرم متفورمین را در روزهای 10-2 بعد از تولد دریافت کردند. برای بررسی حافظه فضایی ، آزمایش ماز آبی موریس 36 روز پس از تولد انجام شد. پس از آزمون رفتاری ، رنگ­آمیزی نیسل برای ارزیابی سلولهای دچار نکروز انجام شد. نتایج بیانگر این است که درمان با متفورمین می­تواند به طور قابل توجهی اختلال در حافظه مکانی را بهبود بخشد (01/0 p <) و همچنین کاهش معنی­دار نورون­های دچار نکروز در گروه درمان با متفورمین در مقایسه با گروه اتانول شد (01/0 p <). بر اساس یافته­ها، متفورمین سبب بهبود اختلال در حافظه فضایی در نوزادان موش قرار گرفته در معرض اتانول می­شود و از مرگ نکروتیک نورون­های هیپوکمپ به طور قابل توجهی جلوگیری می­نماید.

کلیدواژه‌ها


عنوان مقاله [English]

Therapeutic Effect of Metformin on Necrotic Cell Death of Hippocampal Cells and Improvement of Spatial Memory in the Fetal Rat of Model Alcohol Spectrum Disorders

نویسندگان [English]

  • Maryam Sabzali 1
  • Akram Eidi 1
  • Mahdi Khaksari 2
  • Hossin Khastar 2
1 Department of Biology, Islamic Azad University, Science & Research Institute, Tehran, Iran
2 Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
چکیده [English]

Exposure to alcohol during pregnancy causes a wide range of long-term physiological and behavioral effects, collectively referred to as fetal alcohol syndrome (FASD). Nervous disorders due to alcohol abuse in children with apoptosis in several areas of the brain such as the hippocampus is associated with activation of the oxidative-inflammatory cascade and high levels of nerve degeneration. Studies have shown that metformin (1,1-dimethyl hydrochloride), used as a first-line drug for the treatment of type 2 diabetes, can rapidly cross the blood-brain barrier (BBB) ​​and have neuroprotective effects in several diseases of the nervous system. The aim of this study was to assess the protective activities of metformin on memory impairment and neuronal necrosis in the rat hippocampus by postnatal alcohol exposure received by gavage on days 2-10 after birth. Moreover, infants received 20 and 40 mg/kg of metformin on days 2-10 after birth. To assess spatial memory, the Morris water maze test was performed 36 days after birth. After the behavioral test, nickel staining was performed to assess necrotic cells. The results revealed that metformin treatment could significantly improve spatial memory impairment (P <0.01) and significantly reduced necrotic neurons in the metformin treatment group compared to the ethanol group (P <0.01). Metformin has been shown to improve spatial memory impairment in neonatal rats exposed to ethanol and significantly prevent necrotic death of hippocampal neurons.

کلیدواژه‌ها [English]

  • Metformin
  • ethanol
  • spatial memory
  • Necrosis
  • Hippocampus
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