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 (siSMAPoTN), which was distributed only in the intestine and did not diffuse into the whole body after oral administration, was used. siSMAPoTN selectively scavenged intestinal ROS and protected the intestinal environment from damage caused by chronic restraint stress (CRS). In addition, siSMAPoTN suppressed physiological and behavioral depression-related symptoms in the CRS mouse model.
Subject(s)
Depression , Gastrointestinal Microbiome , Mice , Animals , Depression/therapy , Depression/etiology , Reactive Oxygen Species , Brain-Gut Axis , Brain/physiologyABSTRACT
This study describes a technical platform that allows us to measure the pore-forming activity of antimicrobial peptides (AMPs) in the lipid bilayer and estimate antimicrobial activity. We selected six different AMPs of diverse species from urochordata to vertebrata and measured the channel current signals using a microfabricated lipid bilayer system. As a result of the electrophysiological measurements, we were able to estimate the pore-forming activity and roughly predict the antimicrobial activity although there was not a strong correlation between the pore-forming activity and the variety of species. Our method will be a unique tool for analyzing a wide variety of diverse AMPs.
