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磷脂酰胆碱可恢复炎症应激下神经干细胞的神经可塑性。

Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress.

机构信息

Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET) Ocampo y Esmeralda, Predio CONICET and Departamento de Ciencias Biológicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, 2000, Rosario, Argentina.

出版信息

Sci Rep. 2021 Nov 24;11(1):22891. doi: 10.1038/s41598-021-02361-5.

Abstract

The balances between NSCs growth and differentiation, and between glial and neuronal differentiation play a key role in brain regeneration after any pathological conditions. It is well known that the nervous tissue shows a poor recovery after injury due to the factors present in the wounded microenvironment, particularly inflammatory factors, that prevent neuronal differentiation. Thus, it is essential to generate a favourable condition for NSCs and conduct them to differentiate towards functional neurons. Here, we show that neuroinflammation has no effect on NSCs proliferation but induces an aberrant neuronal differentiation that gives rise to dystrophic, non-functional neurons. This is perhaps the initial step of brain failure associated to many neurological disorders. Interestingly, we demonstrate that phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation even under inflammatory stress by modifying the commitment of post-mitotic cells. The pro-neurogenic effect of PtdCho increases the population of healthy normal neurons. In addition, we provide evidences that this phospholipid ameliorates the damage of neurons and, in consequence, modulates neuronal plasticity. These results contribute to our understanding of NSCs behaviour under inflammatory conditions, opening up new venues to improve neurogenic capacity in the brain.

摘要

神经干细胞(NSCs)的生长和分化之间以及神经胶质细胞和神经元分化之间的平衡在任何病理条件下的大脑再生中起着关键作用。众所周知,由于受伤微环境中存在的因素,特别是炎症因子,阻止神经元分化,神经组织在受伤后恢复能力很差。因此,为 NSCs 创造有利条件并促使其分化为功能性神经元是至关重要的。在这里,我们表明神经炎症对 NSCs 的增殖没有影响,但会诱导异常的神经元分化,导致畸形、非功能性神经元。这可能是与许多神经疾病相关的脑衰竭的初始步骤。有趣的是,我们证明富含磷脂酰胆碱(PtdCho)的培养基通过改变有丝分裂后细胞的定向,可以增强神经元分化,即使在炎症应激下也是如此。PtdCho 的促神经发生作用增加了健康正常神经元的数量。此外,我们提供的证据表明,这种磷脂可以改善神经元的损伤,并因此调节神经元的可塑性。这些结果有助于我们理解 NSCs 在炎症条件下的行为,为提高大脑的神经发生能力开辟了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d366/8613233/9fe49ff8b823/41598_2021_2361_Fig1_HTML.jpg

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