Yi-Gan San Restores Behavioral Alterations and a Decrease of Brain Glutathione Level in a Mouse Model of Schizophrenia

Manabu Makinodan,Takahira Yamauchi,Hiroaki Okuda,Miyuki Sadamatsu,Kouko Tatsumi,Yoshinobu Noriyama,Toshifumi Kishimoto,Akio Wanaka

doi:10.4137/jcnsd.s2255

Abstract

The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

Highlights

Yi-gan san (YGS, yokukan-san in Japanese) has been administered to children for the treatment of restlessness and agitation
We investigated whether YGS could restore impaired PPI, methamphetamine hypersensitivity in an open field test and cognitive deficits in a novel object recognition test (NORT)
YGS restored a decrease in prepulse inhibition of Polyinosinicpolycytidilic acid (poly I):C-mice

Summary

Introduction

Yi-gan san (YGS, yokukan-san in Japanese) has been administered to children for the treatment of restlessness and agitation. YGS has only mild sedative effects and induces no EPS, making it a promising candidate as an antipsychotic for schizophrenia. The prepulse inhibition is decreased, the sensitivity to dopamine release is increased, and the cognitive function is impaired in poly I:C-mice.[10,11,12,13] Several reports have shown that the abnormal behaviors were improved by antipsychotic treatments. In this model, we investigated whether YGS could restore impaired PPI, methamphetamine hypersensitivity in an open field test and cognitive deficits in a novel object recognition test (NORT). We measured total glutathione content (both reduced and oxidized species) in whole brain after oral administration of YGS to poly I:C-mice, since the cellular glutathione level is linked to the pathogenesis of schizophrenia[14] and the brain and cerebrospinal fluid glutathione contents were decreased in schizophrenic patients.[15]

Methods

Results

Conclusion