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Astrocyte activation but not neuronal impairment occurs in the hippocampus of mice after 2 weeks of d-galactose exposure.

机译:在D-半乳糖暴露2周后,小鼠海马发生星形细胞活化但不发生神经元损伤。

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AIMS: The objective of this study is to prove that activation of astrocytes precedes neuron cell death in the neurodegenerative process induced by d-galactose (d-gal) exposure. MAIN METHODS: Male adult mice were given intraperitoneal injection of d-gal (200 mg/kg per day) for 2 weeks. The whole brain homogenate and hippocampal sections were then prepared for biochemical analyses, immunohistochemistry and electron microscopy, respectively. KEY FINDINGS: There were no statistically significant differences in brain oxidative and antioxidative parameters between d-gal-treated mice and saline controls. There was also lack of morphological impairment in hippocampal neuronal soma, dendrites and synapses in the model mice. In contrast, hippocampal astrocytes were dramatically activated, and perisynaptic processes of astrocytes were swelling as revealed by ultrastructural analysis. Moreover, d-gal-treated group showed increases in immunostaining levels of glutamate transporter-1 and aquaporin-4 in the hippocampus, which might increase uptake of glutamate from the synaptic cleft into astrocytes. SIGNIFICANCE: These results reveal that astrocytes undergo structural and biochemical changes while no impairment of neuronal elements occurs after 2 weeks of d-gal exposure. Thus, targeting astrocytes may be a promising strategy for the treatment of neurodegenerative diseases at the early stages.
机译:目的:本研究的目的是证明星形胶质细胞的激活在由D-半乳糖(D-加仑)曝光诱导的神经变性过程中的神经元细胞死亡中。主要方法:将男性成人小鼠腹腔注射D-Gal(每天200mg / kg)2周。然后为生物化学分析,免疫组织化学和电子显微镜制备全脑匀浆和海马切片。主要发现:D-GAL处理的小鼠和盐水对照之间的脑氧化和抗氧化参数没有统计学上显着差异。在模型小鼠中,海马神经元躯体,树突和突触缺乏形态损伤。相比之下,海马星形胶质细胞显着激活,并且星形胶质细胞的截面过程溶胀,如超微结构分析所揭示的。此外,D-GAL处理基团显示谷氨酸转运蛋白-1和海马水通道蛋白-4的免疫染色水平的增加,这可能会增加从突触裂缝到星形胶质细胞的谷氨酸的摄取。意义:这些结果表明星形胶质细胞经历了结构性和生化变化,同时在D-GAL暴露后2周后不会发生神经元素的损伤。因此,靶向星形胶质细胞可能是治疗早期阶段神经变性疾病的有希望的策略。

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