title: Ceftriaxone prevents and reverses behavioral and neuronal deficits in an MPTP-induced animal model of Parkinson's disease dementia.
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.
authors.affiliation: Division of Urology, Department of Surgery, Tungs' Taichung Metrohabor Hospital, Taichung 435, Taiwan, ROC.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Occupational Safety and Health Office, Department of Education and Research, Taipei City Hospital, Taipei 10341, Taiwan, ROC.
authors.forename: Ching-Sui
authors.initials: CS
authors.lastname: Hung
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, ROC.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, ROC; Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402, Taiwan, ROC.
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Liao
authors.affiliation: School of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC. Electronic address: gorgeous-1023@hotmail.com.
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Ho
authors.affiliation: School of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC. Electronic address: yjho@csmu.edu.tw.
authors.forename: Ying-Jui
authors.initials: YJ
authors.lastname: Ho
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002443:Ceftriaxone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; C493395:Slc1a2 protein, rat; D002443:Ceftriaxone
keywords: Ceftriaxone; Dementia; Glutamate transporter 1; Glutamatergic hyperactivity; Neuroprotection; Parkinson's disease