Cajanine alleviates anxiety and fear extinction deficits in female mice exposed to single prolonged stress via the ERβ/NF-κB pathway.

Abstract

BACKGROUND: Currently, post-traumatic stress disorder (PTSD) lacks effective treatment strategies. Cajanine has been shown to ameliorate neuroinflammation-related diseases via diverse neuroprotective pathways, indicating its therapeutic potential role for PTSD. OBJECTIVES: This study aimed to explore the effects of cajanine on PTSD and investigate the underlying mechanisms. METHODS: A single prolonged stress (SPS) mouse model was established in mice by conducting psychological, physiological, and chemical stress to mimic PTSD. Cajanine was administered to mice via oral gavage at two doses of 20 and 60 mg/kg. Behavioral assessments included the marble-burying test (MBT), elevated plus maze test (EPMT), and fear memory extinction test (FMET). Expressions of estrogen receptors (ERs) and inflammatory factors in the hippocampus, frontal cortex, and amygdala were quantified via enzyme-linked immunosorbent assay (ELISA) and biochemical assay. RESULTS: SPS induced anxiety-like behaviors and fear memory extinction deficits, along with increased NF-κB, IL-6, and TNF-α expression in the hippocampus, frontal cortex, and amygdala of both the male and female mice. In addition, SPS triggered a reduction in ERβ expression in the hippocampus, frontal cortex, and amygdala of the female mice. Cajanine (60 mg/kg) alleviated the behavioral abnormalities and normalized the overexpression of neuroinflammatory factors and the reduced ERβ level in these brain regions, and this effect was observed only in female SPS mice. Coadministration of cajanine with an ERβ antagonist reversed the beneficial effects of cajanine. of cajanine. CONCLUSION: Cajanine alleviates SPS-induced behavioral deficits in female mice by exerting anti-neuroinflammation effects via ERβ/NF-κB pathway in the hippocampus, cerebral cortex, and amygdala.