اثرات تجویز اسیدفولیک مادر بر بیان mmu-mir-103-1-5p و mtr در قشرمغز نوزادان موش

هدف: با توجه به نقش مهم اسیدفولیک در سنتز و ترمیم dna و تکثیر سلولی و تکوین مغز، در این پروژه به بررسی تاثیر اسیدفولیک (fa) در دوران بارداری بر بیان mmu-mir-103-1-5p و mtr در قشر مغز نوزادان موش بود.  مواد و روش: در مجموع 45 موش باردار به سه گروه با پانزده موش در هر گروه تقسیم شدند. گروه اول و دوم به ترتیب fa با دوزهای 2 و 40 میلی گرم بر کیلوگرم وزن بدن روزانه از طریق گاواژ در تمام دوران بارداری دریافت کردند. گروه سوم fa دریافت نکردند (کنترل). متعاقبا، قشر مغز نوزادان بلافاصله پس از تولد برای آنالیز بیان mmu-mir-103-1-5p و mtr جمع آوری شد. نتایج: نتایج نشان داد که کاهش معنی‌داری در بیان mmu-mir-103-1-5p در دوزهای 2 و 40 نسبت به گروه کنترل وجود دارد. ضمنا، کاهش معنی‌داری در بیان mmu-mir-103-1-5p بین گروه‌های تحت تیمار با fa مشاهده شد. همچنین افزایش معنی‌داری در بیان mtr در دوز 2 نسبت به گروه کنترل وکاهش معنیدار در دوز 40 نسبت به گروه کنترل نشان داد. به‌علاوه کاهش معنی‌داری در بیان mtr بین گروه‌های تحت تیمار با fa مشاهده شد. نتیجه‌گیری: دوز طبیعی fa بیان mmu-mir-103-1-5p را کاهش و بیان mtr را در مقایسه با گروه کنترل افزایش می‌دهد. دوز بالای fa بیان هر دو ژن را در مقایسه با گروه کنترل کاهش می دهد. در نتیجه  fa بیان mmu-mir-103-1-5p و mtr را تغییر می‌دهد و به طور بالقوه بر رشد مغز تاثیر می‌گذارد، در حالی که مقادیر بیش از حد ممکن است تاثیر نامطلوبی داشته باشد.

the effects of maternal folic acid administration on the expression of mmu-mir-103-1-5p and mtr in the cerebral cortex of mouse pups

aim: folate, also known as vitamin b9, is a water-soluble nutrient present in natural food sources. it plays a crucial role in dna synthesis and repair, as well as in methylation reactions. folic acid (fa) is the synthetic form of folate found in enriched foods and supplements. the effects of folate deficiency after birth have not been extensively studied. micrornas (mirnas) are a type of non-coding rnas that play essential roles in regulating gene expression. in recent years, mirnas have been associated with various aspects of brain development, including neurogenesis, neuronal migration, axon and dendrite formation, and synaptogenesis. additionally, altered expression and dysregulation of mirnas have been linked to neurodevelopmental disorders. methionine synthase (mtr) is involved in amino acid metabolism and is responsible for converting the amino acid homocysteine to methionine. mtr is crucial for brain development and is associated with myelin content. this project aimed to investigate the impact of maternal fa supplementation during pregnancy on the expression of mmu-mir-103-1-5p and mtr in the cerebral cortex of mouse pups.materials and methods: a total of 45 pregnant mice were divided into three groups, with 15 mice in each group. the first and second groups received fa at doses of 2 and 40 mg/kg of body weight daily by gavage throughout their entire pregnancy, respectively. the third group did not receive fa and served as the control. subsequently, the cerebral cortex of the offspring was collected immediately after birth for the analysis of mmu-mir-103-1-5p and mtr expression using real-time pcr. statistical analysis was conducted using graphpad prism software.results: in the fa-treated group, the expression of mmu-mir-103-1-5p at a dose of 2 mg/kg body weight was 0.46±0.01, and at a dose of 40 mg/kg body weight, it was 0.27±0.02, whereas in the control group, it was 1.0007±0.03. statistical analysis revealed a significant decrease in mmu-mir-103-1-5p expression at both the 2 mg/kg and 40 mg/kg doses compared to the controls (p<0.0001). furthermore, there was a significant decrease in mmu-mir-103-1-5p expression between the fa-treated groups (p<0.0001). the expression level of mtr in the cerebral cortex was also studied. in the fa-treated groups, the expression at a dose of 2 mg/kg body weight was 1.54±0.04, and at a dose of 40 mg/kg body weight, it was 0.20±0.01, compared to the control group, which was 1.0003±0.02. one-way variance analysis showed a significant increase in mtr expression at the 2 mg/kg dose compared to the controls and a significant decrease at the 40 mg/kg dose compared to the controls (p<0.0001). additionally, there was a significant decrease in mtr expression between the fa-treated groups (p<0.0001).conclusion: it is concluded that the standard dose of fa was found to reduce the expression of mmu-mir-103-1-5p and enhance the expression of mtr when compared to the controls. however, an elevated dose of fa decreases the expression of both genes in comparison to the controls. therefore, fa alters the expression of mmu-mir-103-1-5p and mtr, potentially impacting brain development, while excessive amounts may have an adverse effect.