Chotosan ameliorates cognitive and emotional deficits in an animal model of type 2 diabetes: possible involvement of cholinergic and VEGF/PDGF mechanisms in the brain

BMC Complementary and Alternative Medicine

Research Article

Takako Yokozawa¹  Koichi Tsuneyama²  Takeshi Miyata³  Qi Zhao⁴  Kinzo Matsumoto⁴  Yimin Niu⁴  Ken Tanaka⁵ 

[1] Collaboration Division, Organization for Promotion of Regional Collaboration, University of Toyama, 3190 Gofuku, 930-8555, Toyama, Japan;Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan;Division of Biomedical Informatics, Institute of Natural Medicine, University of Toyama, 930-0194, 2630 Sugitani, Toyama, Japan;Laboratory of Presymptomatic Medical Pharmacology, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, 860-0082, Kumamoto, Japan;Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, 2630, 930-0194, Sugitani, Toyama, Japan;Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan;

关键词: Chotosan;    Diabetes;    Cognitive deficits;    Cholinergic system;    VEGF/PDGF systems;   

DOI  :  10.1186/1472-6882-12-188

 received in 2012-07-02, accepted in 2012-10-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundDiabetes is one of the risk factors for cognitive deficits such as Alzheimer’s disease. To obtain a better understanding of the anti-dementia effect of chotosan (CTS), a Kampo formula, we investigated its effects on cognitive and emotional deficits of type 2 diabetic db/db mice and putative mechanism(s) underlying the effects.MethodsSeven-week-old db/db mice received daily administration of CTS (375 – 750 mg/kg, p.o.) and the reference drug tacrine (THA: 2.5 mg/kg, i.p.) during an experimental period of 7 weeks. From the age of 9-week-old, the animals underwent the novel object recognition test, the modified Y-maze test, and the water maze test to elucidate cognitive performance and the elevated plus maze test to elucidate anxiety-related behavior. After completing behavioral studies, Western blotting and immunohistochemical studies were conducted.ResultsCompared with age-matched non-diabetic control strain (m/m) mice, db/db mice exhibited impaired cognitive performance and an increased level of anxiety. CTS ameliorated cognitive and emotional deficits of db/db mice, whereas THA improved only cognitive performance. The phosphorylated levels of Akt and PKCα in the hippocampus were significantly lower and higher, respectively, in db/db mice than in m/m mice. Expression levels of the hippocampal cholinergic marker proteins and the number of the septal cholinergic neurons were also reduced in db/db mice compared with those in m/m mice. Moreover, the db/db mice had significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2, platelet-derived growth factor-B, and PDGF receptor β, in the hippocampus. CTS and THA treatment reversed these neurochemical and histological alterations caused by diabetes.ConclusionThese results suggest that CTS ameliorates diabetes-induced cognitive deficits by protecting central cholinergic and VEGF/PDGF systems via Akt signaling pathway and that CTS exhibits the anxiolytic effect via neuronal mechanism(s) independent of cholinergic or VEGF/PDGF systems in db/db mice.

【 授权许可】

Unknown   
© Zhao et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.