Application of mRNA technology in neuronal protection of human mature brain-derived neurotrophic factor.

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-04-01 Epub Date: 2025-02-09 DOI:10.1016/j.tice.2025.102788

Liang Wang, Fengjuan Su, Heng Huang, Qiuhong Jiang, Haifang Kong, Zhong Pei

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引用次数: 0

Abstract

Background: Although human mature brain-derived neurotrophic factor (hmBDNF) offers potential neuronal protection, its clinical translation remains challenging. Messenger RNA (mRNA) technology is promising in selectively upregulating protein cleavage products. This proof-of-concept study aims to evaluate the neuronal protective effects of hmBDNF mRNA in vitro.

Methods: We optimized and synthesized hmBDNF mRNA and conducted dose-response and time-response analyses in SH-SY5Y cells. mRNA expression was assessed via qPCR, while protein expression was evaluated through immunostaining and ELISA. Cell survival rate was measured using cell counting kit-8. We examined cell survival rates in both differentiated and non-differentiated SH-SY5Y cells exposed to H2O2 or serum deprivation following hmBDNF mRNA incubation. Additionally, we assessed the expression of synapse-relevant genes (MAP2, synaptophysin) and the mBDNF receptor (TrkB) in both cell types.

Results: The optimized hmBDNF mRNA effectively upregulated hmBDNF expression in SH-SY5Y cells with minimal impact on endogenous proBDNF expression. Dose-response and time-response analyses identified the optimal dose and time point for maximum hmBDNF expression. hmBDNF mRNA significantly increased cell survival in differentiated SH-SY5Y cells expressing MAP2, synaptophysin and TrkB after exposure to oxidative stress or serum deprivation. However, hmBDNF mRNA did not enhance cell survival in non-differentiated SH-SY5Y cells.

Conclusion: The optimized hmBDNF mRNA demonstrated a capacity for neuronal protection in vitro. Further in-vivo studies are required to assess its potential for clinical translation.

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mRNA技术在人成熟脑源性神经营养因子神经元保护中的应用。

背景：虽然人成熟脑源性神经营养因子（hmBDNF）具有潜在的神经元保护作用，但其临床转化仍然具有挑战性。信使RNA （mRNA）技术在选择性上调蛋白裂解产物方面前景广阔。这项概念验证性研究旨在评估hmBDNF mRNA在体外的神经元保护作用。方法：优化合成hmBDNF mRNA，并在SH-SY5Y细胞中进行剂量反应和时间反应分析。采用qPCR检测mRNA表达，免疫染色和ELISA检测蛋白表达。采用细胞计数试剂盒-8测定细胞存活率。我们检测了hmBDNF mRNA孵育后暴露于H2O2或血清剥夺的分化和未分化SH-SY5Y细胞的细胞存活率。此外，我们评估了突触相关基因（MAP2, synaptophysin）和mBDNF受体（TrkB）在两种细胞类型中的表达。结果：优化后的hmBDNF mRNA能有效上调SH-SY5Y细胞中hmBDNF的表达，而对内源性proBDNF的表达影响最小。剂量反应和时间反应分析确定了最大hmBDNF表达的最佳剂量和时间点。hmBDNF mRNA显著提高氧化应激或血清剥夺后表达MAP2、synaptophysin和TrkB的SH-SY5Y分化细胞的细胞存活率。然而，hmBDNF mRNA并没有提高未分化SH-SY5Y细胞的细胞存活率。结论：优化后的hmBDNF mRNA具有一定的体外神经元保护作用。需要进一步的体内研究来评估其临床转化的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.