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水解阿拉伯木聚糖米糠对谷氨酸能爆发活动的调节:在人诱导多能干细胞衍生的神经元和星形胶质细胞中的多电极阵列研究

Modulation of Glutamatergic Burst Activity by Hydrolysed Arabinoxylan Rice Bran: A Multielectrode Array Study in Human-Induced Pluripotent Stem Cell-Derived Neurones and Astrocytes.

作者信息

Puri Basant K, Catuogno-Cal Cecilia, Verduci Ivan

机构信息

Molecular Biology, Cambridge Advanced Research, Cambridge, GBR.

Psychology, Neapolis University Pafos, Pafos, CYP.

出版信息

Cureus. 2025 Jan 20;17(1):e77694. doi: 10.7759/cureus.77694. eCollection 2025 Jan.

DOI:10.7759/cureus.77694
PMID:39834665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11744402/
Abstract

The natural product MGN-3 (Biobran) is a defatted, partially hydrolysed rice bran-derived hemicellulose enzymatically modified with an extract of . It has a high proportion of arabinoxylan. It has a protective action against intracerebroventricular streptozotocin-induced murine sporadic Alzheimer's disease and reverses spatial memory deficit in this disease model. The aim was to test the hypothesis that MGN-3 increases glutamatergic burst activity in human neuronal and glial cells by conducting an in vitro multielectrode array-based micro-electrophysiological study in a cultured mixture of human glutamatergic neurones, GABAergic neurones and astrocytes. The effects of MGN-3 at two concentrations, 0.750 g L and 0.375 g L, and vehicle (control), on glutamatergic burst activity in a triculture of human-induced pluripotent stem cell (hiPSC)-derived GABAergic neurones, glutamatergic neurones and astrocytes were studied. The change in the number of glutamatergic bursts normalised to the vehicle control was analysed using a normal or Gaussian generalised linear model. This statistical model was highly significant ( = 1.468 × 10). Both MGN-3 concentrations were associated with highly significant main effects. These results provide strong evidence to reject the null hypothesis that MGN-3 does not affect glutamatergic burst activity in human neuronal and astrocytic cells. The study's strengths include the novel use of hiPSC-derived neurones and astrocytes and the robust statistical significance of the findings. Limitations include in vitro conditions that may not fully replicate in vivo conditions, potential variability in hiPSC-derived cell preparations, and the need to test other neuronal subtypes or additional doses to assess dose-dependent effects. These should be addressed in future studies.

摘要

天然产物MGN-3(BioBran)是一种脱脂、部分水解的米糠衍生半纤维素,经 提取物酶促修饰而成。它含有高比例的阿拉伯木聚糖。它对脑室内注射链脲佐菌素诱导的小鼠散发性阿尔茨海默病具有保护作用,并能逆转该疾病模型中的空间记忆缺陷。目的是通过在人谷氨酸能神经元、γ-氨基丁酸能神经元和星形胶质细胞的培养混合物中进行基于体外多电极阵列的微电生理研究,来检验MGN-3增加人神经元和神经胶质细胞中谷氨酸能爆发活动的假设。研究了两种浓度(0.750 g/L和0.375 g/L)的MGN-3以及溶剂(对照)对人诱导多能干细胞(hiPSC)衍生的γ-氨基丁酸能神经元、谷氨酸能神经元和星形胶质细胞三培养物中谷氨酸能爆发活动的影响。使用正态或高斯广义线性模型分析归一化至溶剂对照的谷氨酸能爆发数量的变化。该统计模型具有高度显著性( = 1.468 × 10)。两种MGN-3浓度均与高度显著的主效应相关。这些结果提供了有力证据,拒绝MGN-3不影响人神经元和星形胶质细胞中谷氨酸能爆发活动的零假设。该研究的优势包括首次使用hiPSC衍生的神经元和星形胶质细胞以及研究结果具有强大的统计学显著性。局限性包括体外条件可能无法完全复制体内条件、hiPSC衍生细胞制剂存在潜在变异性,以及需要测试其他神经元亚型或额外剂量以评估剂量依赖性效应。这些问题应在未来的研究中加以解决。

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