title: Synergistic effects of ceftriaxone and erythropoietin on neuronal and behavioral deficits in an MPTP-induced animal model of Parkinson's disease dementia.
abstract: Both ceftriaxone (CEF) and erythropoietin (EPO) show neuroprotection and cognitive improvement in neurodegenerative disease. The present study was aimed at clarifying whether combined treatment with CEF and EPO (CEF+EPO) had superior neuroprotective and behavioral effects than treatment with CEF or EPO alone in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model. The rats were injected with CEF (5 mg/kg/day), EPO (100 IU/kg/day), or CEF+EPO after MPTP lesioning and underwent the bar-test, T-maze test, and object recognition test, then the brains were taken for histological evaluation. MPTP lesioning resulted in deficits in working memory and in object recognition, but the cognitive deficits were markedly reduced or eliminated in rats treated with CEF or CEF+EPO, with the combination having a greater effect. Lesioning also caused neurodegeneration in the nigrostriatal dopaminergic system and the hippocampal CA1 area and these changes were reduced or eliminated by treatment with CEF, EPO, or CEF+EPO, with the combination having a greater effect than single treatment in the densities of DAergic terminals in the striatum and neurons in the hippocampal CA1 area. Thus, compared to treatment with CEF or EPO alone, combined treatment with CEF+EPO had a greater inhibitory effect on the lesion-induced behavioral and neuronal deficits. To our knowledge, this is the first study showing a synergistic effect of CEF and EPO on neuroprotection and improvement in cognition in a PD rat model. Combined CEF and EPO treatment may have clinical potential for the treatment of the dementia associated with PD.
authors: Department of Pharmacy, Tainan Municipal Hospital, Tainan 701, Taiwan, ROC.
authors: Chiu-Ku
authors: CK
authors: Huang
authors: School of Psychology, Chung Shan Medical University, Taichung 402, Taiwan, ROC; Department of Psychiatry, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors: Yen-Ting
authors: YT
authors: Chang
authors: Laboratory of Experimental Models of Emotional Pathology, Scientific Research Institute of Physiology and Basic Medicine, Federal State Budgetary Scientific Institution, Novosibirsk 630117, Russia.
authors: Tamara G
authors: TG
authors: Amstislavskaya
authors: Laboratory of Experimental Models of Neurodegenerative Processes, Scientific Research Institute of Physiology and Basic Medicine, Federal State Budgetary Scientific Institution, Novosibirsk 630117, Russia.
authors: Maria A
authors: MA
authors: Tikhonova
authors: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors: Chih-Li
authors: CL
authors: Lin
authors: Occupational Safety and Health Office, Taipei City Hospital, Taipei 10341, Taiwan, ROC. Electronic address: bessyhung@gmail.com.
authors: Ching-Sui
authors: CS
authors: Hung
authors: Department of Psychiatry, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC; Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, ROC. Electronic address: ltj3123@ms2.hinet.net.
authors: Te-Jen
authors: TJ
authors: Lai
authors: School of Psychology, Chung Shan Medical University, Taichung 402, Taiwan, ROC; Department of Psychiatry, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC. Electronic address: yjho@csmu.edu.tw.
authors: Ying-Jui
authors: YJ
authors: Ho
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002443:Ceftriaxone / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003704:Dementia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D004921:Erythropoietin; D002443:Ceftriaxone
keywords: Ceftriaxone; Dementia; Erythropoietin; Neuroprotection; Parkinson’s disease; Recognition; Synergistic effect; Working memory