Alleviation of Immobilization Stress or Fecal Microbiota-Induced Insomnia and Depression-like Behaviors in Mice byand Its Supplement.

Abstract

Insomnia (sleeplessness) is a potential symptom of stress-induced depression/anxiety (DA), which induces TNF-α expression. Therefore, this study aimed to examine the effect of()P72, isolated as a strain suppressing lipopolysaccharide-induced expression of TNF-α in Caco2 cells, on DA and insomnia in immobilization stress (IS)- or cultured fecal microbiota (cFM)-treated mice. Oral administration of live or heat-killed P72 (hP72) reduced IS- or cFM-induced DA-like behaviors. They also reduced sleep latency time (SLT) and enhanced sleep duration (SLD). Additionally, P72 upregulated γ-aminobutyric acid (GABA), GABAreceptor α1, serotonin, and 5-HTreceptor expression, which were downregulated by IS or cFM. Hempseed oil (HO) alone was ineffective against IS-induced DA- and insomnia-like behaviors, but its combination with P72 (PH) or hP72 (hPH) showed enhanced efficacy, reducing DA- and insomnia-like behaviors more strongly than P72 or HO alone. These also reduced the number of NF-κB-positive cells and the expression of TNF-α in the prefrontal cortex and colon. These results imply that P72 and its combination with HO can alleviate DA and insomnia by upregulating serotonergic and GABAergic systems through the suppression of NF-κB signaling.