Facchinetti Roberta, Valenza Marta, Gomiero Chiara, Mancini Giulia Federica, Steardo Luca, Campolongo Patrizia, Scuderi Caterina
Department of Physiology and Pharmacology "Vittorio Erspamer", SAPIENZA University of Rome-P. le Aldo Moro, 5, 00185 Rome, Italy.
Epitech Research Group, 35030 Padova, Italy.
Biomedicines. 2022 May 26;10(6):1236. doi: 10.3390/biomedicines10061236.
Oligodendrocytes are cells fundamental for brain functions as they form the myelin sheath and feed axons. They perform these critical functions thanks to the cooperation with other glial cells, mainly astrocytes. The astrocyte/oligodendrocyte crosstalk needs numerous mediators and receptors, such as peroxisome proliferator-activated receptors (PPARs). PPAR agonists promote oligodendrocyte precursor cells (OPCs) maturation in myelinating oligodendrocytes. In the Alzheimer's disease brain, deposition of beta-amyloid (Aβ) has been linked to several alterations, including astrogliosis and changes in OPCs maturation. However, very little is known about the molecular mechanisms. Here, we investigated for the first time the maturation of OPCs co-cultured with astrocytes in an in vitro model of Aβ toxicity. We also tested the potential beneficial effect of the anti-inflammatory and neuroprotective composite palmitoylethanolamide and luteolin (co-ultra PEALut), which is known to engage the isoform alfa of the PPARs. Our results show that Aβ triggers astrocyte reactivity and inflammation and reduces the levels of growth factors important for OPCs maturation. Oligodendrocytes indeed show low cell surface area and few arborizations. Co-ultra PEALut counteracts the Aβ-induced inflammation and astrocyte reactivity preserving the morphology of co-cultured oligodendrocytes through a mechanism that in some cases involves PPAR-α. This is the first evidence of the negative effects exerted by Aβ on astrocyte/oligodendrocyte crosstalk and discloses a never-explored co-ultra PEALut ability in restoring oligodendrocyte homeostasis.
少突胶质细胞是脑功能的基础细胞，因为它们形成髓鞘并为轴突提供营养。它们通过与其他神经胶质细胞（主要是星形胶质细胞）合作来执行这些关键功能。星形胶质细胞/少突胶质细胞的相互作用需要多种介质和受体，如过氧化物酶体增殖物激活受体（PPARs）。PPAR激动剂可促进少突胶质前体细胞（OPCs）成熟为有髓鞘形成能力的少突胶质细胞。在阿尔茨海默病大脑中，β-淀粉样蛋白（Aβ）的沉积与多种改变有关，包括星形胶质细胞增生和OPCs成熟的变化。然而，关于其分子机制知之甚少。在这里，我们首次在Aβ毒性的体外模型中研究了与星形胶质细胞共培养的OPCs的成熟情况。我们还测试了抗炎和神经保护复合物棕榈酰乙醇胺和木犀草素（联合超PEALut）的潜在有益作用，已知该复合物可作用于PPARs的α亚型。我们的结果表明，Aβ引发星形胶质细胞反应性和炎症，并降低对OPCs成熟重要的生长因子水平。少突胶质细胞确实表现出低细胞表面积和很少的分支。联合超PEALut通过一种在某些情况下涉及PPAR-α的机制，抵消了Aβ诱导的炎症和星形胶质细胞反应性，从而保留了共培养少突胶质细胞形态。这是Aβ对星形胶质细胞/少突胶质细胞相互作用产生负面影响的首个证据，并揭示了联合超PEALut在恢复少突胶质细胞内环境稳定方面从未被探索过的能力。
