欧蛋白通过PPARα依赖和独立途径促进神经可塑性和神经保护
Foteini Malliou1, Christina E Andriopoulou1, Aristeidis Kofinas1
1Department of Pharmacology, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece.
Biomedicines
|August 26, 2023
概括
欧蛋白 (OLE) 通过对大脑衍生神经营养因子 (BDNF) 和其受体TrkB进行上调来增强前额叶皮层的神经可塑性,主要是通过过氧体增殖器激活受体α (PPARα) 激活. 这表明对认知功能的潜在好处.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 橄的关键化合物欧蛋白 (OLE) 具有抗氧化,低脂和心脏保护作用.
- 在神经细胞中,OLE激活过氧体增殖器激活受体α (PPARα),从而提供对脑缺血的保护.
- 神经可塑性对认知功能至关重要,其调节是治疗干预的目标.
研究的目的:
- 研究OLE对神经可塑性指数的影响,重点关注PPARα的作用.
- 探索OLE对神经营养因素和信号通路的影响背后的分子机制.
- 评估OLE的神经保护潜力,独立于PPARα激活.
主要方法:
- 对129/Sv野生型 (WT) 和Pparα-null小鼠进行OLE治疗,持续3周.
- 分析大脑衍生神经营养因子 (BDNF),TrkB,NT3和NT4/5在前额叶皮质 (PFC) 和海马体中的表达.
- 研究ERK1/2,AKT和PKA/CREB信号通路的激活.
- 对分化的人类SH-SY5Y细胞对β-粉样蛋白和H2O2毒性的OLE神经保护的评估.
主要成果:
- 慢性LE治疗通过ERK1/2,AKT和PKA/CREB通路在WT小鼠的PFC中调节了BDNF和TrkB.
- 这些OLE诱导对BDNF和TrkB的影响是PPARα依赖的,因为它们没有在Pparα-null小鼠中观察到.
- 在任何一个大脑区域,OLE都没有改变NT3或NT4/5水平,但纤维酸 (PPARα激动剂) 确实调节了这些因素.
- 在SH-SY5Y细胞中,OLE证明了独立于PPARα的毒性的神经保护.
结论:
- 通过PPARα介导的BDNF和TrkB的上调,OLE增强了突触功能和可塑性,特别是在PFC中,通过PPARα介导的BDNF和TrkB.
- 通过通过PPARα依赖和独立的机制调节神经可塑性,OLE可以提供认知益处.
- 对OLE和类似化合物的进一步研究可能会导致对认知障碍的新疗法策略.
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