Zhang Yunlong, Zhang Xiuping, Qu Shaogang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Mol Neurobiol. 2015 Aug;52(1):78-92. doi: 10.1007/s12035-014-8845-z. Epub 2014 Aug 12.
Ceftriaxone has been shown to attenuate the dopaminergic neuron death and alleviate behavioral disorders in Parkinson's disease models via upregulation of glutamate transporter-1 (GLT-1) and decreases in extracellular glutamate. However, details of how this neuroprotection occurs are uncertain. We hypothesized that cytoprotection by ceftriaxone in astrocytes exposed to 1-methyl-4-phenylpyridinium (MPP(+)) involves suppression of the NF-κB/JNK/c-Jun signaling pathway. Here, we observed a protective effect of ceftriaxone in primary astrocytes exposed to MPP(+). Ceftriaxone enhanced glutamate uptake and promoted primary astrocyte viability after MPP(+) exposure. Ceftriaxone enhances glutamate uptake via upregulation of GLT-1 in the plasma membrane, and alleviates MPP(+)-induced neurotoxicity via suppression of NF-κB/JNK/c-Jun signaling. Collectively, our data offer evidence that increased expression and function of GLT-1 are involved in the protective mechanism of ceftriaxone in astrocytes exposed to MPP(+) in vitro, and we offer insight into the potential therapeutic role of ceftriaxone in treatment of Parkinson's disease.
在帕金森病模型中，头孢曲松已被证明可通过上调谷氨酸转运体-1（GLT-1）和降低细胞外谷氨酸水平来减轻多巴胺能神经元死亡并缓解行为障碍。然而，这种神经保护作用的具体机制尚不清楚。我们推测，头孢曲松对暴露于1-甲基-4-苯基吡啶离子（MPP(+)）的星形胶质细胞的细胞保护作用涉及抑制NF-κB/JNK/c-Jun信号通路。在此，我们观察到头孢曲松对暴露于MPP(+)的原代星形胶质细胞具有保护作用。头孢曲松增强了谷氨酸摄取，并在MPP(+)暴露后促进了原代星形胶质细胞的活力。头孢曲松通过上调质膜上的GLT-1增强谷氨酸摄取，并通过抑制NF-κB/JNK/c-Jun信号通路减轻MPP(+)诱导的神经毒性。总体而言，我们的数据表明，GLT-1表达和功能的增加参与了头孢曲松在体外对暴露于MPP(+)的星形胶质细胞的保护机制，并且我们深入了解了头孢曲松在帕金森病治疗中的潜在治疗作用。
