Chotosan, a Kampo Formula, Ameliorates Hippocampal LTD and Cognitive Deficits in Juvenile-Onset Diabetes Rats

Sachie Sasaki-Hamada; Keita Tamaki; Hayuma Otsuka; Tatsuto Ueno; Hiroaki Sacai; Yimin Niu; Kinzo Matsumoto; Jun-Ichiro Oka

doi:10.1254/jphs.13179FP

This article has now been updated. Please use the final version.

Chotosan, a Kampo Formula, Ameliorates Hippocampal LTD and Cognitive Deficits in Juvenile-Onset Diabetes Rats

Sachie Sasaki-Hamada, Keita Tamaki, Hayuma Otsuka, Tatsuto Ueno, Hiroaki Sacai, Yimin Niu, Kinzo Matsumoto, Jun-Ichiro Oka

Author information

Sachie Sasaki-Hamada
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Keita Tamaki
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Hayuma Otsuka
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Tatsuto Ueno
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Hiroaki Sacai
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Yimin Niu
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan
Kinzo Matsumoto
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan
Jun-Ichiro Oka
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan

Keywords: chotosan, working memory, hippocampal synaptic plasticity, NR2B subunit, streptozotocin-induced diabetes

JOURNAL FREE ACCESS Advance online publication

Article ID: 13179FP

DOI https://doi.org/10.1254/jphs.13179FP

The final version of this article is now available: Vol. 124 (2014), No. 2 pp. 192-200

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Abstract

Childhood-onset type 1 diabetes is associated with modest impairments in cognition and has an elevated risk of cognitive decline. Our previous study showed that working memory and hippocampal long-term depression (LTD) were impaired in juvenile-onset diabetes mellitus (JDM) rats. In this study, we investigated the effect of chotosan (CTS), a traditional herbal formula called a Kampo medicine, which has been clinically demonstrated to be effective for the treatment of vascular dementia, on JDM rats. The repeated treatment with CTS (1 g/kg per day) for 3 – 7 days restored spatial working memory and hippocampal LTD in JDM rats. The expression level of NR2B glutamate receptor subunits, but not other glutamate receptor subunits was enhanced in the hippocampus of JDM rats, and repeated treatment with CTS reversed these changes. These results suggest that CTS improves diabetes-induced cognitive deficits by modulating NMDA-receptor subunit expression.

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