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

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-kappa B/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-kappa B/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.