Ceftriaxone對MPTP所誘發巴金森氏症失智動物模型在行為及神經受損之預防及治療效果

Ceftriaxone Prevents and Reverses Behavioral and Neuronal Deficits MPTP-induced in Animal Model of Parkinson’s Disease Dementia

何詩君(Shih-Chun Ho)

指導教授 ： 何應瑞

中山醫學大學/醫學科技學院/心理學系暨臨床心理學碩士班/碩士(2013年)

摘要

無資料

關鍵字

巴金森氏症 ； 失智症 ； ceftriaxone ； 麩氨酸轉運子 ； 神經保護

並列摘要

A high percentage of patients with Parkinson’s disease (PD) suffer from not only motor dysfunction but also dementia, Parkinson’s disease dementia (PDD). Hyperactivity of glutamatergic system has been observed in PD. Ceftriaxone, a beta-lactam antibiotic, shows neuroprotection by increasing expression of glutamte transporter 1 (GLT-1). GLT-1, one of the major glutamate transporters on astrocytes, is responsible for reuptake of synaptic glutamate. This study was aimed at clarifying whether ceftriaxone prevents or reverses behavioral and neuronal deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model.
Male Wistar rats were stereotaxically administered with MPTP, bilaterally infused into the substantia nigra pars compacta (SNc), to induce PD rat model. Ceftriaxone (100 and 200 mg/kg/day, i.p.) was administered, starting from either 5 days before or 3 days after the MPTP lesioning. All animals were subjected to behavioral tests and then the brains were taken for histological evaluation. One day after the MPTP lesioning, motor dysfunctions in bar test were observed. Such impairments were spontaneously recovered to control level 7 days after the lesioning. In addition, MPTP lesioning resulted in deficits in working memory and object recognition in the T-maze test and object recognition task, respectively. These deficits were not observed in rats receiving pre- and after-treatment with ceftriaxone.
Histologically, MPTP caused neurodegeneration in nigrostrital dopaminergic system and in the hippocampus and induced hyperactivity of glutamatergic system in the subthalamic nucleous, which were suppressed by ceftreiaxone treatment. Moreover, increase of GLT-1 expression and its colocalization with astrocytes were observed in the striatum and hippocampus. These results suggest that, by increasing GLT-1 expression, ceftriaxone prevents and reverses PD-related neurodegeneration and cognitive dysfunctions. Thus, ceftriaxone may have clinical potential for prevention and treatment of dementia associated with PD.

並列關鍵字

Parkinson’s disease ； dementia ； ceftriaxone ； GLT-1 ； neuroprotection

參考文獻

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