健康血浆外泌体对甲基丙二酸诱导的海马神经元损伤具有潜在的神经保护作用
健康血浆外泌体对甲基丙二酸诱导的海马神经元损伤具有潜在的神经保护作用
摘要
外泌体在缓解神经功能缺损和延缓记忆衰退方面显示出良好的潜力，但外泌体的神经保护作用仍然未知。甲基丙二酸血症是一种代谢性疾病，其特点是甲基丙二酸（MMA）在各种组织中积累，抑制神经元的存活和功能，导致神经功能加速衰退。目前尚缺乏缓解这些症状的有效疗法。本研究的目的是探索血浆外泌体对细胞和 MMA 诱导损伤的小鼠模型的神经保护作用。我们评估了血浆外泌体减少神经元凋亡、穿过血脑屏障以及影响与神经元功能相关的各种参数的能力。MMA促进了细胞凋亡，破坏了代谢平衡，改变了B细胞淋巴瘤-2（Bcl-2）、Bcl2相关X（Bax）和突触素-1（Syp-1）的表达，这些变化可能与MMA诱导的神经元凋亡有关。此外，血浆外泌体还能使学习和记忆正常化，并防止 MMA 诱导的神经元凋亡。我们的研究结果表明，神经功能缺陷与甲基丙二酸血症的发病机制有关，而健康的血浆外泌体可能会通过改变外泌体microRNA的表达来发挥神经保护和治疗作用，从而促进这种遗传性代谢疾病的神经元功能恢复。静脉注射血浆外泌体治疗可能是治疗甲基丙二酸血症的一种新型临床治疗策略。
本文章由计算机程序翻译，如有差异，请以英文原文为准。
Healthy Plasma Exosomes Exert Potential Neuroprotective Effects against Methylmalonic Acid-Induced Hippocampal Neuron Injury.
Exosomes have shown good potential for alleviating neurological deficits and delaying memory deterioration, but the neuroprotective effects of exosomes remain unknown. Methylmalonic acidemia is a metabolic disorder characterized by the accumulation of methylmalonic acid (MMA) in various tissues that inhibits neuronal survival and function, leading to accelerated neurological deterioration. Effective therapies to mitigate these symptoms are lacking. The purpose of this study was to explore the neuroprotective effects of plasma exosomes on cells and a mouse model of MMA-induced injury. We evaluated the ability of plasma exosomes to reduce the neuronal apoptosis, cross the blood-brain barrier, and affect various parameters related to neuronal function. MMA promoted cell apoptosis, disrupted the metabolic balance, and altered the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and synaptophysin-1 (Syp-1), and these changes may be involved in MMA-induced neuronal apoptosis. Additionally, plasma exosomes normalized learning and memory and protected against MMA-induced neuronal apoptosis. Our findings indicate that neurological deficits are linked to the pathogenesis of methylmalonic acidemia, and healthy plasma exosomes may exert neuroprotective and therapeutic effects by altering the expression of exosomal microRNAs, facilitating neuronal functional recovery in the context of this inherited metabolic disease. Intravenous plasma-derived exosome treatment may be a novel clinical therapeutic strategy for methylmalonic acidemia.
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