title: 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.
authors.affiliation: School of Psychology, Chung Shan Medical University, Taichung, Taiwan, ROC; Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Ho
authors.affiliation: Department of Pediatrics, Tungs' Taichung Metrohabor Hospital, Taichung, Taiwan, ROC.
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Cornelius Rainer
authors.initials: CR
authors.lastname: Pawlak
authors.affiliation: Laboratory of Biological Psychiatry, State Research Institute of Physiology and Fundamental Medicine SB RAMS, Novosibirsk, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Tikhonova
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Psychiatry, Chung Shan Medical University Hospital, Chung Shan Medical University, Taiwan, ROC.
authors.forename: Te-Jen
authors.initials: TJ
authors.lastname: Lai
authors.affiliation: Laboratory of Biological Psychiatry, State Research Institute of Physiology and Fundamental Medicine SB RAMS, Novosibirsk, Russia. Electronic address: amstislavskaya@yandex.ru.
authors.forename: Tamara G
authors.initials: TG
authors.lastname: Amstislavskaya
authors.affiliation: School of Psychology, Chung Shan Medical University, Taichung, Taiwan, ROC; Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan, ROC. Electronic address: yjho@csmu.edu.tw.
authors.forename: Ying-Jui
authors.initials: YJ
authors.lastname: Ho
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002443:Ceftriaxone / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D065842:Pars Compacta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology
chemical_list: D000978:Antiparkinson Agents; D002443:Ceftriaxone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Ceftriaxone; Cognition; Dementia; Glutamatergic hyperactivity; Neuroprotection; Parkinson's disease