β-Glucan Pretreatment Attenuates Single Prolonged Stress-Associated Behavioural and Neuroinflammatory Changes in Male...

Post-traumatic stress disorder (PTSD) is a severe psychiatric disease with limited options for prevention. Neuroinflammation is a key factor in PTSD pathogenesis. Innate immune preconditioning, the prior mild stimulation of microglia, can induce tolerance to PTSD. Because β-glucan is a natural polysaccharide found in fungal cell walls that can stimulate microglia, we investigated whether β-glucan preconditioning can prevent PTSD-like behaviors in the single prolonged stress (SPS) male mouse model. A single intraperitoneal injection of β-glucan (10 and 20, but not 5 mg/kg) one day before SPS significantly prevented SPS-induced increases in contextual and cued fear freezing, as well as anxiety-like behaviors in the elevated plus maze and open field tests. β-glucan (20 mg/kg) administered 1 or 5 days before SPS maintained its protective effects, but this effect was lost at a 10-day interval. Notably, a second injection 10 days after the first and 1 day before SPS, or four daily injections ending 10 days before SPS, also prevented SPS-induced fear- and anxiety-like behaviors. After the final behavioral tests at the end of the SPS model recovery period, β-glucan pretreatment was found to prevent SPS-induced upregulation of tumor necrosis factor-α (Tnf-α), interleukin-1β (Il-1β), and Il-6 mRNA in the brain. Additionally, pharmacological inhibition (minocycline) or depletion (PLX3397) of microglia abolished β-glucan's behavioral and neuroinflammatory protection. These findings demonstrate that β-glucan, likely through stimulation of microglia, prevents PTSD-like behaviors and attenuates neuroinflammatory responses. As β-glucan can be obtained naturally, it may be a potential drug for preventing PTSD-like behaviors, at least in animals.