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Astrocytic nutritional dysfunction associated with hypoxia-induced neuronal vulnerability in stroke-prone spontaneously hypertensive rats.
Neurochemistry international ( IF 4.2 ) Pub Date : 2020-06-21 , DOI: 10.1016/j.neuint.2020.104786
Kazuo Yamagata 1
Affiliation  

Stroke-prone spontaneously hypertensive rats (SHRSP) is a valuable animal model to investigate human strokes. SHRSP Izumo strain (Izm) neurons are highly sensitive to blood supply changes. Furthermore, SHRSP/Izm astrocytes show various abnormalities upon hypoxic stimulation compared to control Wistar Kyoto (WKY/Izm) rats. This study aimed to describe stroke-related characteristics of SHRSP/Izm-derived neurons and astrocytes. In addition, we discuss the role of astrocytes in the development of stroke in SHRSP/Izm model. In SHRSP/Izm, neuronal death is induced upon reoxygenation after hypoxia. Furthermore, it was shown that SHRSP/Izm astrocytes show significantly reduced lactate production and supply ability to nerve cells when subjected to hypoxic stimulation. In particular, decreased lactate production and monocarboxylic acid transporter (MCT) expression in SHRSP/Izm astrocytes are factors that induce neuronal cell death. Remarkable differences in glial cell line-derived neurotrophic factor (GDNF) expression and L-serine production were also observed in SHRSP/Izm-derived astrocytes compared to WKY/Izm. Reduced production of both GDNF and L-serine contributes to diminished neuronal survival. The differences between SHRSP/Izm and WKY/Izm astrocyte cellular properties may contribute to compromised neuronal nutrition and induction of neuronal death. These properties are likely to be the factors that enhance stroke in SHRSP/Izm.



中文翻译:

与缺氧诱导的自发性高血压大鼠的神经元脆弱性相关的星形胶质细胞营养功能障碍。

中风倾向自发性高血压大鼠 (SHRSP) 是研究人类中风的有价值的动物模型。SHRSP 出云株 (Izm) 神经元对血液供应变化高度敏感。此外,与对照 Wistar Kyoto (WKY/Izm) 大鼠相比,SHRSP/Izm 星形胶质细胞在缺氧刺激下显示出各种异常。本研究旨在描述 SHRSP/Izm 衍生神经元和星形胶质细胞的中风相关特征。此外,我们讨论了星形胶质细胞在 SHRSP/Izm 模型中中风发展中的作用。在 SHRSP/Izm 中,缺氧后再充氧时会诱导神经元死亡。此外,表明 SHRSP/Izm 星形胶质细胞在受到缺氧刺激时显示出显着降低的乳酸产生和神经细胞的供应能力。特别是,SHRSP/Izm 星形胶质细胞中乳酸生成减少和单羧酸转运蛋白 (MCT) 表达是诱导神经元细胞死亡的因素。与 WKY/Izm 相比,在 SHRSP/Izm 衍生的星形胶质细胞中也观察到神经胶质细胞系衍生的神经营养因子 (GDNF) 表达和 L-丝氨酸产生的显着差异。GDNF 和 L-丝氨酸的产生减少导致神经元存活率降低。SHRSP/Izm 和 WKY/Izm 星形胶质细胞特性之间的差异可能导致神经元营养受损和神经元死亡的诱导。这些特性很可能是增加 SHRSP/Izm 中风的因素。与 WKY/Izm 相比,在 SHRSP/Izm 衍生的星形胶质细胞中也观察到神经胶质细胞系衍生的神经营养因子 (GDNF) 表达和 L-丝氨酸产生的显着差异。GDNF 和 L-丝氨酸的产生减少导致神经元存活率降低。SHRSP/Izm 和 WKY/Izm 星形胶质细胞特性之间的差异可能导致神经元营养受损和神经元死亡的诱导。这些特性很可能是增加 SHRSP/Izm 中风的因素。与 WKY/Izm 相比,在 SHRSP/Izm 衍生的星形胶质细胞中也观察到神经胶质细胞系衍生的神经营养因子 (GDNF) 表达和 L-丝氨酸产生的显着差异。GDNF 和 L-丝氨酸的产生减少导致神经元存活率降低。SHRSP/Izm 和 WKY/Izm 星形胶质细胞特性之间的差异可能导致神经元营养受损和神经元死亡的诱导。这些特性很可能是增加 SHRSP/Izm 中风的因素。

更新日期:2020-07-05
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