title: Ceftriaxone prevents the neurodegeneration and decreased neurogenesis seen in a Parkinson's disease rat model: An immunohistochemical and MRI study.
abstract: Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Department of Medical Imaging, Chung Shan Medical University Hospital, ​Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors.forename: Jun-Cheng
authors.initials: JC
authors.lastname: Weng
authors.affiliation: Laboratory of Experimental Models of Neurodegenerative Processes, Federal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine", Novosibirsk 630117, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Tikhonova
authors.affiliation: School of Physical Therapy, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors.forename: Jian-Horng
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors.forename: Mei-Shiuan
authors.initials: MS
authors.lastname: Shen
authors.affiliation: Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors.forename: Wan-Yun
authors.initials: WY
authors.lastname: Meng
authors.affiliation: Department of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
authors.forename: Yen-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Psychology, National Taiwan University, Taipei 10617, Taiwan, ROC.
authors.forename: Ke-Hsin
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Psychology, National Taiwan University, Taipei 10617, Taiwan, ROC; Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 10617, Taiwan, ROC.
authors.forename: Keng-Chen
authors.initials: KC
authors.lastname: Liang
authors.affiliation: Occupational Safety and Health Office, Taipei City Hospital, Taipei 10341, Taiwan, ROC. Electronic address: bessyhung@gmail.com.
authors.forename: Ching-Sui
authors.initials: CS
authors.lastname: Hung
authors.affiliation: Laboratory of Experimental Models of Emotional Pathology, Federal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine", Novosibirsk 630117, Russia. Electronic address: amstislavskaya@yandex.ru.
authors.forename: Tamara G
authors.initials: TG
authors.lastname: Amstislavskaya
authors.affiliation: Department 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: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D001973:Bromodeoxyuridine / Q000378:metabolism; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D020267:MPTP Poisoning / Q000150:complications* / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013223:Statistics as Topic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D002443:Ceftriaxone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D003576:Electron Transport Complex IV; D001973:Bromodeoxyuridine
keywords: BrdU; Ceftriaxone; MEMRI; Neurodegeneration; Neurogenesis; Parkinson’s disease