اثر ایمی‌پرامین بر اختلال حافظه در موش صحرایی مدل بیماری آلزایمر: دخالت مسیر سیگنالینگ انسولین و پروتئین Reelin

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 استادیار، گروه علوم جانوری، دانشکده علوم زیستی، دانشگاه خوارزمی، تهران، ایران

2 کارشناسی ارشد، گروه علوم جانوری، دانشکده علوم زیستی، دانشگاه خوارزمی، تهران، ایران

چکیده

مقاله پژوهشی




مقدمه: بیماری آلزایمر، یک اختلال عصبی پیشرونده‌ است که باعث مختل شدن عملکردهای شناختی می‌شود. ایمی‌پرامین، نوعی داروی ضدافسردگی با اثرات آنتی‌اکسیدانی و ضدالتهابی در مغز می‌باشد. هدف از مطالعه‌ی حاضر، بررسی اثر ایمی‌پرامین بر اختلال حافظه با تمرکز بر مسیر سیگنالینگ انسولین و شکل‌پذیری سیناپسی در موش‌های صحرایی تیمار شده با استرپتوزوتوسین (Streptozotocin) STZ بود.
روش‌ها: در مطالعه‌ی تجربی حاضر، 32 سر موش صحرایی نر نژاد ویستار در 4 گروه شاهد،STZ ،STZ +ایمی‌پرامین و ایمی‌پرامین قرار گرفتند. القاء مدل حیوانی بیماری آلزایمر با تزریق درون بطنی STZ (mg/kg3؛ μl3 در هر بطن) انجام گرفت. تست ماز بعلاوه‌ی شکل مرتفع و آزمون یادگیری اجتنابی غیرفعال جهت بررسی عملکردهای شناختی مورد استفاده قرار گرفتند. 24ساعت بعد از تزریق STZ، تیمار با ایمیپرامین (mg/kg20) به صورت داخل صفاقی و به مدت 14 روز انجام گرفت. بررسی میزان بیان ژن انسولین و فاکتورهای دخیل در مسیر سیگنالینگ انسولین (IR، IRS2، PI3K، Akt و mTOR) توسط تکنیک Real-time PCR و ارزیابی سطح پروتئین Reelin (فاکتور دخیل در شکل‌پذیری سیناپسی) توسط تکنیک وسترن بلات انجام شد. جهت تجزیه و تحلیل داده‌ها از آزمون آنالیز واریانس یک‌طرفه و آزمون تعقیبی Tukey استفاده شد.
یافته‌ها: نتایج نشان داد که  STZمنجر به بروز اختلالات حافظه در موش‌ها شد و بیان ژن انسولین، فاکتورهای دخیل در مسیر سیگنالینگ انسولین و نیز سطح پروتئین Reelin را کاهش داد. در حالی‌که ایمی‌پرامین، سبب کاهش اختلالات حافظه و نیز افزایش بیان فاکتورهای مذکور در هیپوکامپ حیوانات تیمار شده با STZ گردید.
نتیجه‌گیری: به نظر می‌رسد، ایمی‌پرامین از طریق تأثیر بر مسیر سیگنالینگ انسولین و پروتئین دخیل در شکل‌پذیری سیناپسی سبب کاهش اختلالات حافظه در حیوانات تیمار شده با STZ می‌گردد.

تازه های تحقیق

المیرا بیرامی:  PubMed ,Google Scholar

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of Imipramine on Memory Disorder in a Rat Model of Alzheimer’s Disease: Involvement of Insulin Signaling Pathway and Reelin Protein

نویسندگان [English]

  • Elmira Beirami 1
  • Delaram Eslimi Esfahani 1
  • Alireza Jamshidi Hasanabadi 2
1 Assistant Professor, Department of Animal Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran
2 MSc, Department of Animal Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran
چکیده [English]

Background: Alzheimer's disease (AD) is a progressive neurological disorder that impairs cognitive functions. Imipramine is an antidepressant drug with antioxidant and anti-inflammatory effects on the brain. The present study aimed to investigate the effect of imipramine on memory impairment, focusing on insulin signaling pathway and synaptic plasticity in rats treated with streptozotocin (STZ).
Methods: In this experimental study, 32 male Wistar rats were divided into 4 groups: control, STZ, STZ+imipramine, and imipramine. An animal model of AD was induced by intraventricular injection of STZ (3mg/kg; 3μl/ventricle). Elevated plus maze and passive avoidance tests were used to examine cognitive functions. 24 h after STZ injection, treatment with imipramine (20mg/kg) was done intraperitoneally for 14 days. The expression level of insulin and the factors involved in the insulin signaling pathway (IR, IRS2, PI3K, Akt, and mTOR) were investigated by Real-time PCR and the protein level of Reelin (a factor involved in synaptic plasticity) was evaluated by western blot technique. One-way analysis of variance and Tukey's post hoc test were used to analyze the data.
Findings: The results showed that STZ caused memory disorders in rats and decreased the expression level of insulin and factors involved in the insulin signaling pathway, and also the protein level of Reelin. In contrast, imipramine reduced memory disorders and increased the expression of the mentioned factors in the hippocampus of animals treated with STZ.
Conclusion: Imipramine appears to reduce memory disorders in STZ-treated animals through its effects on the insulin signaling pathway and protein involved in synaptic plasticity.

کلیدواژه‌ها [English]

  • Imipramine
  • Alzheimer's disease
  • Memory disorders
  • Insulin
  • Reelin protein
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