Ceftriaxone ameliorates motor deficits and protects dopaminergic neurons in 6-hydroxydopamine-lesioned rats

ACS Chem Neurosci. 2012 Jan 18;3(1):22-30. doi: 10.1021/cn200072h. Epub 2011 Oct 26.

Abstract

Parkinson's disease is caused by the degeneration of dopaminergic neurons in substantia nigra. There is no current promising treatment for neuroprotection of dopaminergic neurons. Ceftriaxone is a beta-lactam antibiotic and has been reported to offer neuroprotective effects (Rothstein, J.-D., Patel, S., Regan, M.-R., Haenggeli, C., Huang, Y.-H., Bergles, D.-E., Jin, L., Dykes, H.-M., Vidensky, S., Chung, D.-S., Toan, S.-V., Bruijn, L.-I., Su, Z.-Z., Gupta, P., and Fisher, P.-B. (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature433, 73-77). In the present study, efficacy of ceftriaxone in neuroprotection of dopaminergic neurons and amelioration of motor deficits in a rat model of Parkinson's disease were investigated. Ceftriaxone was administrated in 6-hydroxydopamine-lesioned rats. Using behavioral tests, grip strength and numbers of apomorphine-induced contralateral rotation were declined in the ceftriaxone-treated group. More importantly, cell death of dopaminergic neurons was found to decrease. In addition, both the protein expression and immunoreactivity for GLT-1 were up-regulated. The present results strongly indicate that ceftriaxone is a potential agent in the treatment of Parkinson's disease.

Keywords: Animal model of Parkinson’s disease; antibiotic; basal ganglia; ceftriaxone; degeneration of dopaminergic neurons; glutamate transporter; glutamate transporter subtype 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Blotting, Western
  • Brain / drug effects*
  • Brain / pathology
  • Ceftriaxone / pharmacology*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Female
  • Motor Activity / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / pathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Neuroprotective Agents
  • Ceftriaxone
  • Oxidopamine