مرور نظامند استراتژی های داروئی بر پایه سیستم سروتونرژیک برای کنترل دیسکینزی ناشی از ال-دوپا در موشهای صحرائی پارکینسونی
A systematic review of therapeutic strategies based on the serotonergic system for management of the L‐DOPA‐Induced dyskinesias in hemiparkinsonian rats
مجریان: جواد محمودی
خلاصه روش اجرا: With no time restriction, we will undertake an electronic search of computer bibliographic databases of MEDLINE via PubMed, Embase, Google Scholar, and Proquest using the keywords “6-hydroxydopamine”, “dyskinesias”, “L- DOPA”, “serotonergic”, and “rat”. Also, we will manually search the bibliographies of retrieved articles in order not to miss any reports in this regard. Two independent investigators will screen the title, abstract, and where necessary full text based on the inclusion and exclusion criteria. All disagreements will be resolved by the third investigator
اطلاعات کلی طرح 
| مرحله جاری طرح | خاتمه قرارداد و اجرا |
| کد طرح | 61131 |
| عنوان فارسی طرح | مرور نظامند استراتژی های داروئی بر پایه سیستم سروتونرژیک برای کنترل دیسکینزی ناشی از ال-دوپا در موشهای صحرائی پارکینسونی |
| عنوان لاتین طرح | A systematic review of therapeutic strategies based on the serotonergic system for management of the L‐DOPA‐Induced dyskinesias in hemiparkinsonian rats |
| نوع طرح | طرح تحقیقاتی |
| اولویت طرح | سالمندی (پارکینسون، آلزایمر و استئوپروز) |
| نوع مطالعه | مطالعات مرور سیستماتیک |
| تحقیق در نظام سلامت | بلی |
| آیا طرح پایاننامه دانشجویی است؟ | خير |
| مقطع پایان نامه | |
| مدت اجرا - ماه | 10 |
| نوآوری و ضرورت انجام تحقیق | Levodopa (L-DOPA) is by far the most effective therapeutic option for Parkinson’s disease (PD). Although a well-tolerated medication, L-DOPA induces abnormal involuntary movements (AIMs) in several patients following chronic exposure, commonly known as levodopa-induced dyskinesia (LID) (1). The mechanisms by which L-DOPA induces motor fluctuations are yet unclear. Several studies have confirmed the role of serotonergic raphe-striatal neurons in L-DOPA-induced LID (2, 3). Evidence suggests that serotonergic neurons of the central nervous system (CNS) convert orally administered L-DOPA to dopamine (4). These neurons may have a role in the dysregulated metabolism of exogenous L-DOPA leading to the aberrant striatal release of dopamine in PD patients and LID (5, 6). Studies performed on rodents and primates have found that modulation of serotonergic activity using 5-HT receptor type 1A and 1B (5-HT1A and 5-HT1B ) agonists such as buspirone and eltoprazine, acute 5-HT transporter (SERT) blockade, or elimination of serotonin (5-HT) afferent terminals reduced the severity of LID without exacerbating PD manifestations (7-10). Although these strategies have yielded promising results in the laboratory, their effects have not been investigated in the clinic. This might be due to the uncertainty about the impacts of these medications in PD patients. Pre-clinical animal studies play a crucial role in the development of novel therapeutics for human via providing evidence for design of clinical trials (11). However, we increasingly become aware of the limitations and weaknesses of our pre-clinical studies all of which cause failure during replication of the results from bench to bedside. This is known as “reproducibility crisis” (12). Systematic reviews of animal studies are detailed, comprehensive, and planned search of the available literature aimed at answering a particular question and reducing bias via detecting and classifying all relevant data (13). Although systematic reviews of clinical data are extensively available, there exists a paucity regarding the pre-clinical studies (11). It has been proposed that systematic reviews can increase the so-called “experimental rigor” and quality of the animal studies and improve translational studies reproducibility (14). This systematic review aimed at finding the old and most up-to-date serotonergic system-based therapeutics for L-DOPA‐induced dyskinesia in hemiparkinsonian rats. Given, the increasing number of patients suffering from LID, the present study may propose new therapeutic options in this regard. |
| اهداف اختصاصی | Identification of the serotonergic system-based regimens for L-DOPA‐induced dyskinesia in hemiparkinsonian rats. - Determination of the doses of serotonergic system-based regimens for L-DOPA‐induced dyskinesia in hemiparkinsonian rats. - Determination of the administration time course of serotonergic system-based regimens for L-DOPA‐induced dyskinesia in hemiparkinsonian rats. |
| چکیده انگلیسی طرح | .Our search will be limited to publications in English and other (i.e., non-human) animals. We will included all experimental studies on rat reported in full-text publications or conference papers which used 6-hydroxydopamine to induce PD, L-DOPA as a treatment for PD, and serotonergic system-based therapeutics for the attenuation of LID. The primary outcome measure will be to find all serotonergic system-based therapeutics used for LID and the secondary outcome measure will be to assess their effects in this regard. We will exclude studies not using rat (those on mice and primates) and those using models other than 6-hydroxydopamine (those induced with MPTP). We will also exclude all ex vivo or in vitro (primary culture or cell line) studies. Non-serotonergic system-based therapeutics (i.e., glutaminergic, adrenergic, etc.) used for the treatment of LID will be also excluded. The methodological quality of the included studies will be assessed using a modified version of the CAMARADES’ study quality checklist. This checklist includes items such as statement of inclusion and exclusion of animals from the study, blinded assessment of outcome, sample-size calculation, and publication in peer-reviewed journal, randomization to treatment or control, statement of compliance with regulatory requirements, allocation concealment, and statement regarding possible conflict of interest |
| کلمات کلیدی | Parkinson’s disease: A neurodegenerative disorders associated with nigrostriatal dopaminergic deficits L-dopa induced dyskinesia: state refers to abnormal motor appearance seen in Parkinsonian patients under L-dopa regimen Serotonergic system: A neuronal pathway that stems from the raphe nucleus and innervates structures like striatum |
| ذینفعان نتایج طرح |
اطلاعات مجری و همکاران
| نام و نامخانوادگی | سمت در طرح |
|---|---|
| جواد محمودی | مجری اول (اصلی-هیات علمی) |
| فرشته فرج دخت | همکار اصلی |
| فریبا پاشازاده | همکار اصلی |
| علیرضا مجدی | همکار اصلی |
| سعید صدیق اعتقاد | همکار اصلی |
اطلاعات تفضیلی
| حوزه خبر | خبر |
|---|---|
| رسانه ها و مردم | عنوان خبر متن خبر |
| متخصصان و پژوهشگران | عنوان خبر تنظیم سیستم سروتونرژیک مغزی می تواند بر اختلالات حرکتی ناشی از مصرف لوودوپا در بیماران پارکینسونی موثر باشدمتن خبر سیستم سروتونرژیک بدنبال مرگ نورونهای دوپامینی در بیماری پارکینسون فعال شده و از طریق پدیده ای به نام هم انتقالی جبرانی، از لوودوپای مصرفی توسط بیماران، دوپامین مورد نیاز را برای تنظیم فعالیت های سیستم حرکتی مغز تامین می کند. مرور نظام مند حاضر نشان داد که تنظیم فعالیت سیستم سروتونرژیک از طریق گیرنده های سروتونرژیک تیپ A و سروتونرژیک تیپ B می تواند تولید و آزاد سازی دوپامین تولید شده توسط سیستم سروتونرژیک را به گونه ای تعدیل نماید که در طولانی مدت، از عوارض حرکتی داروی ضد پارکینسونی موسوم به لوودوپا در افراد مبتلا به بیماری پارکینسون بکاهد و کیفیت زندگی این افراد بهبود دهد. |
| سیاستگذاران درمانی | عنوان خبر متن خبر |
| سیاستگذاران پژوهشی | عنوان خبر متن خبر |
| لینک (URL) مقاله انگلیسی مرتبط منتشر شده 1 |
