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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2012

Open Access 01-12-2012 | Research article

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

Authors: Qi Zhao, Yimin Niu, Kinzo Matsumoto, Koichi Tsuneyama, Ken Tanaka, Takeshi Miyata, Takako Yokozawa

Published in: BMC Complementary Medicine and Therapies | Issue 1/2012

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Abstract

Background

Diabetes 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.

Methods

Seven-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.

Results

Compared 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.

Conclusion

These 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.
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Metadata
Title
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
Authors
Qi Zhao
Yimin Niu
Kinzo Matsumoto
Koichi Tsuneyama
Ken Tanaka
Takeshi Miyata
Takako Yokozawa
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2012
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-12-188

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