Direct evidence for the involvement of intestinal reactive oxygen species in the progress of depression via the gut-brain axis

Yutaka Ikeda; Naoki Saigo; Yukio Nagasaki

doi:10.1016/j.biomaterials.2023.122053

Direct evidence for the involvement of intestinal reactive oxygen species in the progress of depression via the gut-brain axis

Biomaterials. 2023 Apr:295:122053. doi: 10.1016/j.biomaterials.2023.122053. Epub 2023 Feb 17.

Authors

Yutaka Ikeda¹, Naoki Saigo¹, Yukio Nagasaki²

Affiliations

¹ Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
² Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Center for Research in Isotopes and Environmental Dynamics (CRiED), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan. Electronic address: happyhusband@nagalabo.jp.

PMID: 36821954
DOI: 10.1016/j.biomaterials.2023.122053

Abstract

Depression is a serious global social problem. Various therapeutic drugs have been developed based on the monoamine hypothesis; however, treatment-resistant depression is a common clinical issue. Recently, the gut-brain axis, which is associated with the hypothesis that the intestinal environment affects the brain, has garnered significant interest, and several studies have attempted to treat brain disorders based on this axis. These attempts include fecal transplantation, probiotics and prebiotics. In this study, we focused on intestinal reactive oxygen species (ROS) because excessive ROS levels disturb the intestinal environment. To elucidate the impact of scavenging intestinal ROS on depression treatment via the gut-brain axis, a novel polymer-based antioxidant (siSMAPo^TN), which was distributed only in the intestine and did not diffuse into the whole body after oral administration, was used. siSMAPo^TN selectively scavenged intestinal ROS and protected the intestinal environment from damage caused by chronic restraint stress (CRS). In addition, siSMAPo^TN suppressed physiological and behavioral depression-related symptoms in the CRS mouse model.

Keywords: Depression; Gut-brain axis; Leaky gut; Oxidative stress; Polymer-based antioxidant; TEMPO.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / physiology
Brain-Gut Axis
Depression* / etiology
Depression* / therapy
Gastrointestinal Microbiome*
Mice
Reactive Oxygen Species

Substances

Reactive Oxygen Species