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Ceftriaxone Protects Astrocytes from MPP+ via Suppression of NF-κB/JNK/c-Jun Signaling

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Abstract

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.

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Abbreviations

GLT-1:

glutamate transporter-1

MPP+ :

1-methyl-4-phenylpyridinium

GFAP:

glial fibrillary acidic protein

PD:

Parkinson’s disease

PI3K:

phosphatidylinositol 3-kinase

NF-κB:

nuclear factor-κB

CDK4:

cyclin-dependent kinase 4

JNK:

c-Jun N-terminal kinases

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Acknowledgments

This work was supported by grants from the Science and Technology Planning Project of Guangdong Province (2012B050200003) and the Science and Technology Planning Project of Guangzhou (2013J4500018).

Conflict of Interests

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China

    Yunlong Zhang & Shaogang Qu

  2. Teaching Center of Experimental Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China

    Xiuping Zhang

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  1. Yunlong Zhang
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Correspondence to Shaogang Qu.

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Zhang, Y., Zhang, X. & Qu, S. Ceftriaxone Protects Astrocytes from MPP+ via Suppression of NF-κB/JNK/c-Jun Signaling. Mol Neurobiol 52, 78–92 (2015). https://doi.org/10.1007/s12035-014-8845-z

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