Molecular changes evoked by the beta-lactam antibiotic ceftriaxone across rodent models of substance use disorder and neurological disease. (August 2020)

• Record Type: Journal Article
• Authors: Smaga, Irena; Fierro, Daniel; Mesa, Javier; Filip, Malgorzata; Knackstedt, Lori A
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 115(2020)
• Page Start: 116
• Page End: 130
• Publication Date: 2020-08
• Subjects: ALS -- Huntington's disease -- Parkinson's disease -- Alzheimer's disease -- Ischemia -- Seizure -- Glutamate -- Dopamine -- System xc- -- Cocaine -- Alcohol -- Opioid; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2020.05.016
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Ceftriaxone (200 mg/kg for minimum 2 days) consistently restores GLT-1 expression. In healthy rodents ceftriaxone only reliably upregulates GLT-1 in the hippocampus. Increased GLT-1 expression does not consistently arise from increased transcription. Ceftriaxone alters expression of other proteins that accompany neurological disease. Abstract: Ceftriaxone is a beta-lactam antibiotic that increases the expression of the major glutamate transporter, GLT-1. As such, ceftriaxone ameliorates symptoms across multiple rodent models of neurological diseases and substance use disorders. However, the mechanism behind GLT-1 upregulation is unknown. The present review synthesizes this literature in order to identify commonalities in molecular changes. We find that ceftriaxone (200 mg/kg for at least two days) consistently restores GLT-1 expression in multiple rodent models of neurological disease, especially when GLT-1 is decreased in the disease model. The same dose given to healthy/drug-naive rodents does not reliably upregulate GLT-1 in any brain region except the hippocampus. Increased GLT-1 expression does not consistently arise from transcriptional regulation, and is likely to be due to trafficking changes. In addition to altered transporter expression, ceftriaxone ameliorates neuropathologies (e.g. tau, amyloid beta, cell death) and aberrant protein expression associated with a number of neurological disease models. Taken together, these results indicate that ceftriaxone remains a strong candidate for treatment of multiple disorders in the clinic.