Razi Journal of Medical Sciences

fa تاثیر تمرین تناوبی شدید و ژل رویال بر بیان ژن‌های مرتبط با حافظه (CREB و TrKB) در هیپوکمپ موش‌های دیابتی نوع دوم The Effect of HIIT and Royal Jelly on the Expression of Memory-Related Genes (CREB and TrKB) in the Hippocampus of Type 2 Diabetic Rats فیزیولوژی ورزش Exercise Physiology پژوهشي Research <div style="text-align: justify;"><a name="_Hlk184301929">زمینه و هدف:</a> دیابت نوع دو شایع‌ترین بیماری غدد درون‌ریز است که به دلیل عدم تحمل گلوکز در اثر برهم‌ خوردن تعادل بین ذخایر و تقاضای انسولین رخ می‌دهد. هدف پژوهش حاضر، تعیین تاثیر تمرین تناوبی شدید و ژل رویال بر بیان ژنهای مرتبط با حافظه (CREB و TrKB) در هیپوکمپ موشهای دیابتی نوع دوم بود. روش کار: روش انجام تحقیق آزمایشی حاضر بدین صورت بود که 36 سر موش نر ویستار چهار الی 6 هفته‌ای (20±110 گرم) بعد از دو هفته آشنایی با محیط جدید و رسیدن به وزن 20±193 گرم به مدت 5 ماه تا رسیدن به میانگین وزنی حدود 50±409 گرم با رژیم پر چرب (45 تا 60 درصد چربی) تغذیه شده و با تزریق درون صفاقی 25  میلیگرم بر کیلوگرم وزن بدن استرپتوزوتوسین (STZ- Streptozotocin) دیابتی شده و به صورت تصادفی به‌ ٤ گروه کنترل دیابتی‌ (٨ سـر)، تمرین‌ تنـاوبی‌ شـدید (١٠سـر)، ژل رویـال (٨ سـر)، تمرین‌ تناوبی‌ شدید و ژل رویال (١٠ سر) تقسیم شدند. گروه تمرین و تمرین- ژل رویال، تمرین تناوبی شدید را به صورت پنج جلسه در هفته با افزایش تدریجی تناوب شدید از سرعت 30 تا 36 متر در دقیقه (80 تا 95 درصد Vo2max) و تناوب استراحت یک دقیقه ای با سرعت 16 تا 22 متر در دقیقه (50 تا 56 درصد Vo2max) و زمان 15 تا 33 دقیقه به‌صورت دویدن روی تردمیل برای مدت دو ماه (8 هفته) انجام دادند. ژل رویال با دوز 100 میلیگرم بر کیلوگرم رقیق شده در آب مقطر و به روش گاواژ 5 روز در هفته به گروه ژل رویال و ژل رویال – تمرین قبل شروع تمرین داده شد. یافته‌ها: نتایج نشان داد بیان ژنهای <a name="_Hlk182771386">CREB</a> و TrKB بافت هیپوکمپ مغز موشها در گروههای تجربی تمرین، ژل رویال و تمرین-ژل رویال افزایش معناداری یافت (0001/0=P). نتیجهگیری: استفاده از تمرین تناوبی شدید همراه با ژل رویال زیر نظر متخصص به افراد دیابتی توصیه میشود.</div> <div style="text-align: justify;"> Background & Aim: Type 2 diabetes is the most common endocrine disease that occurs due to glucose intolerance as a result of the imbalance between insulin reserves and demand. One of the most common complications of diabetes is diabetic neuropathy. Cognitive disorders caused by damage to hippocampal neurons are also complications of diabetes, and memory and cognition deficits are reported to be more common in diabetic people than in non-diabetic people. The hippocampus is one of the most sensitive areas of the brain to metabolic disorders, including diabetes. During diabetes, the hippocampus undergoes neurophysiological, structural and molecular changes, such as a decrease in neurogenesis and hippocampal disintegration. Diabetes causes inflammation in the brain. Managing diabetes and controlling the risks of diabetes can be done in different ways. Regular sports activity can have a major contribution in reducing the complications of diabetes, including obesity, high blood pressure, hyperlipidemia, and increasing insulin sensitivity in the target tissue.  Sports activity increases hippocampal memory and learning and increases hippocampal neurogenesis. Also, sports activity activates various pathways of neurogenesis, which leads to an increase in neural plasticity and is associated with strengthening learning and memory. CREB is a BDNF transcription factor that plays an important role in neuron protection and improving learning and memory, By binding to specific tyrosine kinase receptors, BDNF triggers intracellular cascades and finally produces and differentiates new neurons. Two different groups of these tyrosine kinase receptors that can bind to neurotrophins include P75 and TrKB. Previous research suggests that exercise training may affect the expression of CREB and TrKB genes.  Royal jelly and its biologically active compounds have received attention due to their antioxidant effects and antibacterial, anti-diabetic, anti-cancer, anti-inflammatory, anti-blood pressure, and immune system drugs. Understanding the relationship between exercise, royal jelly and the reduction of diabetes-related complications such as Alzheimer's would be beneficial for public health. The aim of the present study was to investigate the effect of HIIT and royal jelly on the expression of memory-related genes (CREB and TrKB) in the hippocampus of type 2 diabetic rats. Methods: The statistical population of this study consisted of 36 four-week-old male Wistar rats (110±20 grams). The test samples were kept for two weeks with the aim of familiarization with the environment and reached the weight range of 193 ± 20 grams. All mice were fed with a high-fat diet (45-60% fat) for 5 months. Rats had unlimited access to food and water was available in 500 ml bottles in all cages.And after the rats became obese and reached an average weight of 407±50 grams, to create a type 2 diabetes, STZ was injected into them at a low dose of 25 milligram per kilogram of body weight by intraperitoneal injection. One week after the induction of diabetes, fasting blood glucose was measured and blood sugar above 150 to 400 mg/dL was considered as a criterion to ensure that the mice had type 2 diabetes. To further ensure that the mice became diabetic and the accuracy of the work, blood was taken from 10 mice randomly from the tail and their glucose was measured. Then type 2 diabetic rats were divided into 4 diabetic control groups (8 rats), HIIT (10 rats), royal jelly (8 rats), HIIT and royal jelly (10 rats) so that their weight averages are close to each other. At the end of the protocol, 29 rats remained in 4 diabetic control groups (6),HIIT(8), royal jelly (7),HIIT and royal jelly (8). The HIIT protocol consisted of eight weeks of aerobic exercise, five sessions per week with a gradual increase in extreme frequency from 30 to 36 meters per minute(80 to 95% of the maximum oxygen consumption)  and a rest period of 16 to 22 (50 to 56% of the maximum oxygen consumption) meters per minute for 15 to 33 minutes by running on a treadmill. Running time increased from 15 minute s in the first week to 33 minutes in the eighth week. Royal jelly with a dose of 100 mg/kg diluted in distilled water was given by gavage 5 days a week to the royal gel and royal gel-HIIT groups, pre-workout. At the end of the training period and 48 hours after the last training session of the experimental groups, sampling was performed after 12 hours of fasting. Measurement of hippocampal tissue gene expression was performed using Real-time PCR. Finally, one-way and post hoc analysis of variance were used to analyze the research hypotheses and compare the groups, and two-factor test and effect size index were used to determine the effectiveness of each factor. Results: The results of the study showed that the expression of CREB and TrKB genes in the hippocampal tissue of the rat brain increased in the experimental groups of exercise, royal jelly, and exercise-royal jelly, and their changes were significant (P=0.0001). Conclusion: In general, according to the results of the study, it can be concluded that high-intensity interval training (HIIT) and royal jelly have a significant effect on TrkB and CREB gene expression in the hippocampus. HIIT training affects BDNF production in the brain in several ways: First, HIIT increases mitochondrial activity and ROS concentration in neurons, which ROS causes CREB-BDNF transcription and signaling. Second, HIIT increases calcium ion concentration in neurons, which increases CaMKII activity and causes MAPK ERK MSK signaling to activate CREB-BDNF transcription and neural plasticity. Intracellular calcium can also increase ROS production in neurons. ROS can activate CREB-BDNF transcription, and finally, HIIT increases systemic blood lactate concentration, thereby enhancing NMDA receptor activity to increase intracellular calcium ion concentration in neurons. Therefore, intense interval training can prevent hippocampal tissue degradation caused by diabetes, and royal jelly, due to its diverse vitamin and protein compounds and phenolic compounds, as well as its multiple antioxidant and anti-inflammatory roles, increases neurogenesis and reduces oxidative damage in brain tissue. By reducing factors such as oxidative stress, inflammation, and increasing the secretion of neurotrophins and neurogenesis, the beneficial effects of exercise and royal jelly on brain structure and function, especially the diabetic hippocampus, which is susceptible to damage, can be achieved.</div> تمرین تناوبی شدید, هیپوکمپ, موش‌های چاق دیابتی HIIT, Royal Jelly, Hippocampus, Obese Diabetic Mice 1 11 http://rjms.iums.ac.ir/browse.php?a_code=A-10-5008-9&slc_lang=fa&sid=1 Leila Marefat لیلا معرفت 3900319475328460088058 0009-0004-0206-8540 No PhD Student of Exercise Physiology, Science and Research Branch, Islamic Azad University, Department Physical Education and Sport Science, Tehran, Iran دانشجوی دکتری تخصصی فیزیولوژی ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران Hossein Abed natanzi حسین عابدنطنزی abednazari@gmail.com 3900319475328460088059 3900319475328460088059 Yes Assistant Professor of Exercise Physiology, Science and Research Branch, Islamic Azad University, Department Physical Education and Sport Science, Tehran, Iran استادیار، گروه تربیت بدنی و علوم ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران Mandana Gholami ماندانا غلامی 3900319475328460088060 3900319475328460088060 No Associate Professor of Exercise Physiology, Science and Research Branch, Islamic Azad University, Department Physical Education and Sport Science, Tehran, Iran دانشیار، گروه تربیت بدنی و علوم ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران Farshad Ghazalian فرشاد غزالیان 3900319475328460088061 3900319475328460088061 No Associate Professor of Exercise Physiology, Science and Research Branch, Islamic Azad University, Department Physical Education and Sport Science, Tehran, Iran دانشیار، گروه تربیت بدنی و علوم ورزشی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران