title: Protective effect of carnosine on febrile seizures in immature mice.
abstract: Febrile seizures (FSs) are the most common type of convulsions in childhood and complex FSs represent an increased risk for development of temporal lobe epilepsy. The aim of this study was to analyze the anticonvulsant effects of carnosine, an endogenous dipeptide composed of alanine and histidine, on hyperthermia induced seizure in immature mice. Injection of carnosine significantly increased the latency and decreased the duration of FSs in a dose-dependent manner. In addition, histidine had similar effects on FSs as carnosine. The protective effect of carnosine or histidine was completely abolished by α-fluoromethylhistidine (α-FMH), a selective and irreversible histidine decarboxylase inhibitor, or in histidine decarboxylase deficient (HDC-KO) mice. Peripheral carnosine administration increased the level of carnosine, histidine and histamine in the cortex and hippocampus of mice pups, but decreased glutamate contents in the cortex and hippocampus. These results indicate that carnosine can protect against FSs in mice pups through its conversion to histamine, suggesting that it may serve as an efficient anti-FSs drug in the future.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Yun-Jian
authors.initials: YJ
authors.lastname: Dai
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Deng-Chang
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China. Electronic address: huww@zju.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Hou
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China. Electronic address: chenzhong@zju.edu.cn.
authors.forename: Ceng-Lin
authors.initials: CL
authors.lastname: Xu
authors.affiliation: Department of Engineering, School of Medicine, Tohoku University, Aoba-ku, Sendai 980-8775, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000627:therapeutic use*; D002336:Carnosine / Q000378:metabolism / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006639:Histidine / Q000378:metabolism / Q000627:therapeutic use; D006640:Histidine Decarboxylase / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D003294:Seizures, Febrile / Q000378:metabolism / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D018698:Glutamic Acid; D006639:Histidine; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D002336:Carnosine; D006640:Histidine Decarboxylase
keywords: Carnosine; Febrile seizure; Glutamate; Histamine; Histidine