Neuroprotective effects of ceftriaxone in Poly I:C-induced neuroinflammation in murine hippocampal cultures
Year: 2025
Type: dissertation
Abstract: Neurodegenerative diseases are characterized by the progressive loss of neuronal function and structure, often culminating in cognitive decline. A shared feature across these disorders, despite differences in their pathogenic mechanisms, is neuroinflammation, which involves the persistent activation and death of neurons and glial cells. Notably, the downregulation or dysfunction of the glutamate transporter 1 (GLT-1) has been observed in affected patients and is implicated in inflammation-induced neuronal damage. In this context, infections caused by viral or bacterial pathogens can trigger detrimental proinflammatory responses in central nervous system (CNS) resident immune cells, including microglia and astrocytes, leading to neuronal death and chronic inflammation. Enhancing GLT-1 expression and function emerges as a potential therapeutic strategy to counteract these effects; nevertheless, the precise role of GLT-1 in the early stages of neurodegenerative diseases remains inadequately understood. This study aimed to investigate the positive therapeutic effects of ceftriaxone, a β-lactam antibiotic known to upregulate GLT-1, in attenuating neuroinflammation triggered by polyinosinic:polycytidylic acid (Poly I:C), a model for viral infection. Employing a ternary cell model composed of neurons, microglia, and astrocytes, we demonstrated that Poly I:C stimulation resulted in the release of pro-inflammatory cytokines (TNF-α, IL-6, IL-10), activation of microglia and astrocytes, and a significant downregulation of GLT-1. This downregulation was associated with astrocytic dysfunction, loss of neuronal dendritic spines, and impairment of long-term potentiation (LTP) maintenance. However, treatment with ceftriaxone resulted in a remarkable rescue effect, reversing microglial hypertrophy, restoring GLT-1 expression, and mitigating both dendritic spine loss and LTP dysfunction in neurons. Overall, the findings of this thesis highlight ceftriaxone's promising potential as a therapeutic agent for preventing inflammation-induced damage in the CNS. By targeting GLT-1, ceftriaxone may offer a novel approach to ameliorating neuroinflammatory processes, ultimately contributing to the preservation of neuronal health and cognitive function in the context of neurodegenerative diseases.
Author: Shi, Xizi
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6888927803
Cites:
Cited by:
Related to: