2009 Fiscal Year Final Research Report
Evaluation of Circadian Rhythm Disturbances in Mice Models with Impaired Heme Biosynthesis Induced by Environmental Chemicals
| Project/Area Number |
18590119
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Josai International University |
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Principal Investigator |
MITSUMOTO Atsushi Josai International University, 薬学部, 教授 (00276164)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Yoko 城西国際大学, 薬学部, 助手 (90348178)
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| Co-Investigator(Renkei-kenkyūsha) |
KAWAI Hiroshi 城西国際大学, 薬学部, 講師 (20321854)
ISHIBASHI Takuya 城西国際大学, 薬学部, 助手 (20555825)
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| Research Collaborator |
WATANABE Yukino 城西大学, 大学院・薬学研究科
IWADATE Reiko 慶應義塾大学, 大学院・薬学研究科
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| Project Period (FY) |
2006 – 2009
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| Keywords | 概日リズム / 生物時計 / ポルフィリン症 / ヘム / 環境化学物質 |
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| Research Abstract |
We have developed a mouse model of hepatic porphyria induced by ingestion of a chemical substance, griseofulvin (GF), and analyzed the characterization of biochemical and behavioral phenotypes of the porphyria model mice. The porphyria mice exhibited tremendous accumulation of aminolevurinic acid (ALA) and porphyrins asn heme precursors, and also had symptoms, such as liver injury and skin inflammation. In addition, they exhibited several neurological and psychological behaviors, such as anxiety and depression, typically observed in acute porphyria. Moreover, we found that these mice had differential sensitivities to psychological drugs, such as diazepam, comparing to the control mice, without any difference in the pharmacokinetics. Furthermore, circadian activity and temperature rhythms of these mice exhibited phase-advances by a few hours. The abnormal circadian rhythms were ameliorated by the treatment of heme. In conclusion, we demonstrated heme-regulated abnormality of circadian rhythms in the mice model of hepatic porphyria induced by GF.
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