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

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:115

Review

Smaga, Irena¹  Fierro, Daniel²  Mesa, Javier^2,3  Filip, Malgorzata¹  Knackstedt, Lori A.^2,3 

[1] Polish Acad Sci, Dept Drug Addict Pharmacol, Maj Inst Pharmacol, Smetna 12, PL-31343 Krakow, Poland

[2] Univ Florida, Dept Psychol, 945 Ctr Dr, Gainesville, FL 32611 USA

[3] Univ Florida, Ctr Addict Res & Educ, Gainesville, FL 32611 USA

关键词: ALS;    Huntington's disease;    Parkinson's disease;    Alzheimer's disease;    Ischemia;    Seizure;    Glutamate;    Dopamine;    System xc;    Cocaine;    Alcohol;    Opioid;   

DOI  :  10.1016/j.neubiorev.2020.05.016

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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