Effects of ceftriaxone on the behavioral and neuronal changes in an MPTP-induced Parkinson's disease rat model

Abstract

Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) and treatment with drugs modulating glutamatergic activity may have beneficial effects. Ceftriaxone has been reported to increase glutamate uptake by increasing glutamate transporter expression. The aim of this study was to determine the effects of ceftriaxone on working memory, object recognition, and neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. MPTP was stereotaxically injected into the substantia nigra pars compacta (SNc) of male Wistar rats. Then, starting the next day (day 1), the rats were injected daily with either ceftriaxone (200 mg/kg/day, i.p.) or saline for 14 days and underwent a T-maze test on days 8-10 and an object recognition test on days 12-14. MPTP-lesioned rats showed impairments of working memory in the T-maze test and of recognition function in the object recognition test. The treatment of ceftriaxone decreased the above MPTP-induced cognitive deficits. Furthermore, this study provides evidence that ceftriaxone inhibits MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area. In conclusion, these data support the idea that hyperactivity of the glutamatergic system is involved in the pathophysiology of PD and suggest that ceftriaxone may be a promising pharmacological tool for the development of new treatments for the dementia associated with PD.

Keywords: Ceftriaxone; Cognition; Dementia; Glutamatergic hyperactivity; Neuroprotection; Parkinson's disease.