Neuroprotective Effects of Ceftriaxone Involve the Reduction of Aβ Burden and Neuroinflammatory Response in a Mouse Model of Alzheimer's Disease

Maria A Tikhonova; Tamara G Amstislavskaya; Ying-Jui Ho; Anna A Akopyan; Michael V Tenditnik; Marina V Ovsyukova; Alim A Bashirzade; Nina I Dubrovina; Lyubomir I Aftanas

doi:10.3389/fnins.2021.736786

Neuroprotective Effects of Ceftriaxone Involve the Reduction of Aβ Burden and Neuroinflammatory Response in a Mouse Model of Alzheimer's Disease

Front Neurosci. 2021 Sep 29:15:736786. doi: 10.3389/fnins.2021.736786. eCollection 2021.

Authors

Affiliations

¹ Laboratory of the Experimental Models of Neurodegenerative Processes, Department of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine (SRINM), Novosibirsk, Russia.
² Laboratory of Translational Biopsychiatry, Department of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine (SRINM), Novosibirsk, Russia.
³ Department of Neuroscience, Institute of Medicine and Psychology, Novosibirsk State University, Novosibirsk, Russia.
⁴ Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan.
⁵ Faculty of Life Sciences, Novosibirsk State University, Novosibirsk, Russia.
⁶ Department of Clinical Neuroscience, Behavior and Neurotechnologies, Scientific Research Institute of Neurosciences and Medicine (SRINM), Novosibirsk, Russia.

Abstract

Ceftriaxone (CEF) is a safe and multipotent antimicrobial agent that possesses neuroprotective properties. Earlier, we revealed the restoration of cognitive function in OXYS rats with signs of Alzheimer's disease (AD)-like pathology by CEF along with its modulating the expression of genes related to the system of amyloid beta (Aβ) metabolism in the brain. The aim of this study was to determine the effects of CEF on behavior, Aβ deposition, and associated neuroinflammation using another model of an early AD-like pathology induced by Aβ. Mice were injected bilaterally i.c.v. with Aβ fragment 25-35 to produce the AD model, while the CEF treatment (100 mg/kg/day, i.p., 36 days) started the next day after the surgery. The open field test, T-maze, Barnes test, IntelliCage, and passive avoidance test were used for behavioral phenotyping. Neuronal density, amyloid accumulation, and the expression of neuroinflammatory markers were measured in the frontal cortex and hippocampus. CEF exhibited beneficial effects on some cognitive features impaired by Aβ neurotoxicity including complete restoration of the fear-induced memory and learning in the passive avoidance test and improved place learning in the IntelliCage. CEF significantly attenuated amyloid deposition and neuroinflammatory response. Thus, CEF could be positioned as a potent multipurpose drug as it simultaneously targets proteostasis network and neuroinflammation, as well as glutamate excitotoxicity, oxidative pathways, and neurotrophic function as reported earlier. Together with previous reports on the positive effects of CEF in AD models, the results confirm the potential of CEF as a promising treatment against cognitive decline from the early stages of AD progression.

Keywords: amyloid; behavior; cognition; drug repurposing; microglia; neurodegeneration.