A probiotic NVP1704 alleviates stress-induced sleeplessness/depression-like symptoms in mice by upregulating serotonergic and GABAergic systems and downregulating NF-κB activation

Sleeplessness (insomnia) is a potential symptom of depression. A probiotic NVP1704 alleviates depression-like behavior and neuroinflammation in mice. Therefore, to understand whether NVP1704 could be effective against sleeplessness in vivo, we exposed immobilization stress (IS) in mice, then orally administered NVP1704 for 5 days, and assayed depression/anxiety-like behavior in the open field, elevated plus maze, and tail suspension tests, sleeping latency time, and sleep duration, euthanized then by exposure to CO2, and analyzed their related biomarkers. Oral administration of NVP1704 decreased IS-induced depression/anxiety-like behavior and sleeping latency time and increased IS-suppressed sleeping duration. NVP1704 increased IS-suppressed expression of γ-aminobutyric acid (GABA), GABAA receptor α1 (GABAARα1) and α2 subunits (GABAARα2), serotonin, 5-HT receptors (5-HT1AR and 5-HT1BR), and melatonin receptors (MT1R and MT2R) in the prefrontal cortex and thalamus. NVP1704 also increased the IS-suppressed GABAARα1-positive cell population in the prefrontal cortex and decreased IS-induced corticosterone, TNF-α, and IL-6 expression and the NF-κB+Iba1+ cell population in the brain and myeloperoxidase, TNF-α, and IL-6 expression and the NF-κB+CD11c+ cell population in the colon. Based on these findings, NVP1704 may alleviate depression/anxiety/sleeplessness-like behaviors through the upregulation of serotonergic and GABAergic systems and downregulation of NF-κB activation.