Gamma oryzanol impairs alcohol-induced anxiety-like behavior in mice via upregulation of central monoamines associated with Bdnf and Il-1\u03b2 signaling

Salina Akter,Kazi Rasel Uddin,Yijin Lyu,Hiroyuki Sasaki,Shigenobu Shibata

doi:10.1038/s41598-020-67689-w

Salina Akter, Kazi Rasel Uddin + Show 3 more

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https://doi.org/10.1038/s41598-020-67689-w

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Journal: Scientific Reports	Publication Date: Jun 30, 2020
Citations: 7	License type: open-access

Affiliation: Waseda University

Abstract

Adolescent alcohol exposure may increase anxiety-like behaviors by altering central monoaminergic functions and other important neuronal pathways. The present study was designed to investigate the anxiolytic effect of 0.5% γ-oryzanol (GORZ) and its neurochemical and molecular mechanisms under chronic 10% ethanol consumption. Five-week-old ICR male mice received either control (14% casein, AIN 93 M) or GORZ (14% casein, AIN 93 M + 0.5% GORZ) diets in this study. We showed that GORZ could potentially attenuate alcohol-induced anxiety-like behaviors by significantly improving the main behavioral parameters measured by the elevated plus maze test. Moreover, GORZ treatment significantly restored the alcohol-induced downregulation of 5-hydroxytryptophan and 5-hydroxyindole acetic acid in the hippocampus and improved homovanillic acid levels in the cerebral cortex. Furthermore, a recovery increase in the level of 3-methoxy-4-hydroxyphenylglycol both in the hippocampus and cerebral cortex supported the anxiolytic effect of GORZ. The significant elevation and reduction in the hippocampus of relative mRNA levels of brain-derived neurotrophic factor and interleukin 1β, respectively, also showed the neuroprotective role of GORZ in ethanol-induced anxiety. Altogether, these results suggest that 0.5% GORZ is a promising neuroprotective drug candidate with potential anxiolytic, neurogenic, and anti-neuroinflammatory properties for treating adolescent alcohol exposure.

Highlights

Adolescent alcohol exposure may increase anxiety-like behaviors by altering central monoaminergic functions and other important neuronal pathways
The results indicate that ethanol-exposed control mice had a significant decrease in 5-hydroxyindole acetic acid (5-HIAA) levels in the hippocampus (P < 0.01) and cerebral cortex (P < 0.05), compared to the water-exposed control mice; the anxiety level would likely be higher in ethanol-exposed control mice (Fig. 3B,G)
To gain insight into a possible neural mechanism of 0.5% GORZ that could mediate chronic alcohol consumption-induced anxiety-like behaviors, we examined Bdnf mRNA expression in the hippocampus and cerebral cortex (Fig. 4A,C)

Summary

Introduction

Adolescent alcohol exposure may increase anxiety-like behaviors by altering central monoaminergic functions and other important neuronal pathways. The significant elevation and reduction in the hippocampus of relative mRNA levels of brain-derived neurotrophic factor and interleukin 1β, respectively, showed the neuroprotective role of GORZ in ethanol-induced anxiety. These results suggest that 0.5% GORZ is a promising neuroprotective drug candidate with potential anxiolytic, neurogenic, and anti-neuroinflammatory properties for treating adolescent alcohol exposure. Chronic ethanol consumption during adolescence may alter the risk/reward assessment and damage the developing brain, leading to an increase in impulsivity[4]. Chronic alcohol consumption is related with an increase in production of pro-inflammatory cytokines, such as IL1-β, due to the sensitization of immune c ells[22]

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