Chotosan, a Kampo Formula, Ameliorates Chronic Cerebral Hypoperfusion-Induced Deficits in Object Recognition Behaviors and Central Cholinergic Systems in Mice

元データ 2007-04-20 社団法人 日本薬理学会

概要

We previously demonstrated that the Kampo formula chotosan (CTS) ameliorated spatial cognitive impairment via central cholinergic systems in a chronic cerebral hypoperfusion (P2VO) mouse model. In this study, the object discrimination tasks were used to determine if the ameliorative effects of CTS on P2VO-induced cognitive deficits are a characteristic pharmacological profile of this formula, with the aim of clarifying the mechanisms by which CTS enhances central cholinergic function in P2VO mice. The cholinesterase inhibitor tacrine (THA) and Kampo formula saikokeishito (SKT) were used as controls. P2VO impaired object discrimination performance in the object recognition, location, and context tests. Daily administration of CTS (750 mg/kg, p.o.) and THA (2.5 mg/kg, i.p.) improved the object discrimination deficits, whereas SKT (750 mg/kg, p.o.) did not. In ex vivo assays, tacrine but not CTS or SKT inhibited cortical cholinesterase activity. P2VO reduced the mRNA expression of m3 and m5 muscarinic receptors and choline acetyltransferase but not that of other muscarinic receptor subtypes in the cerebral cortex. Daily administration of CTS and THA but not SKT reversed these expression changes. These results suggest that CTS and THA improve P2VO-induced cognitive impairment by normalizing the deficit of central cholinergic systems and that the beneficial effect on P2VO-induced cognitive deficits is a distinctive pharmacological characteristic of CTS.

著者

TOHDA Michihisa Division of Medical Pharmacology, Institute of Natural Medicine, University of Toyama
渡邉 裕司 富山医科薬科大学和漢薬研究所生物試験部門
Tohda Michihisa 和漢医薬学総合研究所 複合薬物薬理学分野
Tohda Michihisa 富山医科薬科大学和漢薬研究所
Tohda Michihisa 和漢医薬学総合研究所 複合薬物薬理学
MURAKAMI Yukihisa Division of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical
MATSUMOTO Kinzo Division of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical
渡辺 裕司 International Research Center For Traditional Medicine Toyama Prefecture International Health Comple
Murakami Yukihisa 富山大学和漢医薬学総合研究所 複合薬物薬理学
Mukarami Yukihisa Institute Of Natural Medicine Toyama Medical And Pharmaceutical University
Murakami Yukihisa Division Of Medicinal Pharmacology Institute Of Natural Medicine Toyama Medical And Pharmaceutical U
Murakami Yukihisa Research Institute For Wakan-yaku (traditional Sino-japanese Medicines)
SHIMADA Yutaka Department of Japanese Oriental Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical Uni
渡邉 浩司 富山医科薬科大学和漢薬研究所生物試験部門
Obi Ryosuke Department of Japanese Oriental Medicine, Toyama Medical and Pharmaceutical University
Shimada Y Tokyo Inst. Technol. Yokohama Jpn
Murakami Yuko Department Of Bioactive Molecules National Institute Of Infectious Diseases
Tohda Michihisa Division Of Medical Pharmacology Institute Of Natural Medicine University Of Toyama
Tohda Michihisa Department Of Pharmacology Institute Of Natural Medicine (wakan-yaku) Toyama Medical And Pharmaceuti
Matsumoto Kinzo Div. Of Medicinal Pharmacology Inst. Of Natural Medicine Univ. Of Toyama
Matsumoto Kinzo Division Of Medicinal Pharmacology Institute Of Natural Medicine Toyama Medical And Pharmaceutical U
Shimada Yuji Microsystem Research Center Precision And Intelligence Laboratory Tokyo Institute Of Technology
ZHAO Qi Division of Medicinal Pharmacology, Institute of Natural Medicine,University of Toyama
Shimada Y Tohoku Univ. Sendai Jpn
Matsumoto K Div. Of Medicinal Pharmacology Inst. Of Natural Medicine Univ. Of Toyama
Zhao Qi Division Of Medicinal Pharmacology Institute Of Natural Medicine University Of Toyama
Zhao Qi Division Of Pharmacology Institute Of Natural Medicine Toyama Medical & Pharmaceutical Universit
Watanabe H Health Science University Of Hokkaido
嶋田 豊 富山医科薬科大学医学部和漢診療学
Watanabe Hiroshi Radia Industry Co. Ltd
Matsumoto Kinzo 富山大学和漢医薬学総合研究所 複合薬物薬理学
Murakami Y Department Of Bioactive Molecules National Institute Of Infectious Diseases
Obi Ryosuke Division Of Medicinal Pharmacology Institute Of Natural Medicine University Of Toyama:department Of
Obi Ryosuke Department Of Japanese Oriental Medicine Graduate School Of Medical And Pharmaceutical Sciences Univ
Murakami Y Toho Univ. Chiba Jpn
渡邉 裕司 富山医科薬科大学生物試験部門
Tohda M Department Of Pharmacology Institute Of Natural Medicine Toyama Medical And Pharmaceutical Universit
島田 洋蔵 Dept. Of Japanese Oriental Medicine Faculty Of Medicine University Of Toyama
Shimada Yutaka Department Of Anatomy And Cell Biology School Of Medicine Chiba Unversity
Shimada Yutaka Department Of Japanese Oriental Medicine Faculty Of Medicine
Shimada Yutaka 21^<st> Century Coe Program Toyama Medical And Pharmaceutical University
東田 道久 Division Of Medicinal Pharmacology Institute Of Natural Medicine University Of Toyama
Watanabe Hiroshi Biotechnology Laboratory Japan Atomic Energy Research Institute
Shimada Yutaka Department Of Anatomy And Cell Biology School Of Medicine Chiba University

関連論文

▼もっと見る