Ceftriaxone prevents and reverses behavioral and neuronal deficits in an MPTP-induced animal model of Parkinson's disease dementia

Chao Yu Hsu, Ching Sui Hung, Hung Ming Chang, Wen Chieh Liao, Shih Chun Ho, Ying Jui Ho

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Glutamatergic hyperactivity plays an important role in the pathophysiology of Parkinson's disease (PD). Ceftriaxone increases expression of glutamate transporter 1 (GLT-1) and affords neuroprotection. This study was aimed at clarifying whether ceftriaxone prevented, or reversed, behavioral and neuronal deficits in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Male Wistar rats were injected daily with either ceftriaxone starting 5 days before or 3 days after MPTP lesioning (day 0) or saline and underwent a bar-test on days 1-7, a T-maze test on days 9-11, and an object recognition test on days 12-14, then the brains were taken for histological evaluation on day 15. Dopaminergic degeneration in the substantia nigra pars compacta and striatum was observed on days 3 and 15. Motor dysfunction in the bar test was observed on day 1, but disappeared by day 7. In addition, lesioning resulted in deficits in working memory in the T-maze test and in object recognition in the object recognition task, but these were not observed in rats treated pre- or post-lesioning with ceftriaxone. Lesioning also caused neurodegeneration in the hippocampal CA1 area and induced glutamatergic hyperactivity in the subthalamic nucleus, and both changes were suppressed by ceftriaxone. Increased GLT-1 expression and its co-localization with astrocytes were observed in the striatum and hippocampus in the ceftriaxone-treated animals. To our knowledge, this is the first study showing a relationship between ceftriaxone-induced GLT-1 expression, neuroprotection, and improved cognition in a PD rat model. Ceftriaxone may have clinical potential for the prevention and treatment of dementia associated with PD.

Original languageEnglish
Pages (from-to)43-56
Number of pages14
JournalNeuropharmacology
Volume91
DOIs
Publication statusPublished - 2015

Fingerprint

Ceftriaxone
Parkinson Disease
Dementia
Animal Models
Amino Acid Transport System X-AG
Subthalamic Nucleus
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
4-phenyl-1,2,3,6-tetrahydropyridine
Short-Term Memory
Astrocytes
Cognition
Wistar Rats
Hippocampus
Brain

Keywords

  • Ceftriaxone
  • Dementia
  • Glutamate transporter 1
  • Glutamatergic hyperactivity
  • Neuroprotection
  • Parkinson's disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology
  • Medicine(all)

Cite this

Ceftriaxone prevents and reverses behavioral and neuronal deficits in an MPTP-induced animal model of Parkinson's disease dementia. / Hsu, Chao Yu; Hung, Ching Sui; Chang, Hung Ming; Liao, Wen Chieh; Ho, Shih Chun; Ho, Ying Jui.

In: Neuropharmacology, Vol. 91, 2015, p. 43-56.

Research output: Contribution to journalArticle

Hsu, Chao Yu ; Hung, Ching Sui ; Chang, Hung Ming ; Liao, Wen Chieh ; Ho, Shih Chun ; Ho, Ying Jui. / Ceftriaxone prevents and reverses behavioral and neuronal deficits in an MPTP-induced animal model of Parkinson's disease dementia. In: Neuropharmacology. 2015 ; Vol. 91. pp. 43-56.
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