Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.

中文翻译：

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褪黑素通过增加线粒体功能来增强神经干细胞的分化和植入

神经干细胞（NSC）被认为是保护和恢复神经退行性疾病（NDs）（如帕金森氏病和阿尔茨海默氏病（分别为PD和AD））中受损神经元的有前途的治疗方法。但是，新的研究表明，要使该策略有效，就必须进行NSC区分。几项研究表明褪黑激素可增加成熟的神经元标记，这反映了NSC向神经元的分化。然而，尚未完全确定线粒体可能参与了NSC分化过程中褪黑激素的作用。因此，我们测试了褪黑激素对NSC增殖和分化的影响，试图确定这些作用是否取决于调节线粒体的活性。我们测量了增殖和分化标记，线粒体的结构和功能参数以及氧化应激指标，还评估了细胞移植的植入情况。这使我们能够证明褪黑激素（25μM）诱导NSC分化为少突胶质细胞和神经元。这些作用取决于NSCs中线粒体质量/ DNA /复合物的增加，线粒体呼吸作用，膜电位以及ATP合成。有趣的是，褪黑素可防止线粒体活性高水平引起的氧化应激。最后，我们发现褪黑素在移植后可丰富ND小鼠模型中的NSC植入。