Microglia-Dependent Reversal of Depression-Like Behaviors in Chronically Stressed Mice by Administration of a Specific Immuno-stimulant β-Glucan

In recent years, the decline of microglia in the hippocampus has been shown to play a role in the development of depression, and its reversal shows marked antidepressant-like effects. β-glucan is a polysaccharide from Saccharomyces cerevisiae and has numerous beneficial effects on the nervous system, including improving axon regeneration and cognition. Considering its immuno-stimulatory activities in cultured microglia and brain tissues, we hypothesize that β-glucan may be a potential candidate to correct the functional deficiency of microglia and thereby alleviate depression-like behaviors in chronically stressed animals. An expected, our results showed that a single injection of β-glucan 5 h before behavioral tests at a dose of 10 or 20 mg/kg, but not at a dose of 5 mg/kg, reversed the depression-like behavior induced by chronic stress in mice in the tail suspension test, forced swimming test, and sucrose preference test. The effect of β-glucan (20 mg/kg) also showed time-dependent properties that were statistically significant 5 and 8, but not 3, hours after drug injection and persisted for at least 7 days. Fourteen days after β-glucan injection, no antidepressant-like effect was observed anymore. However, this effect was overcome by a second β-glucan injection (20 mg/kg) 14 days after the first β-glucan injection. Stimulation of microglia appeared to mediate the antidepressant-like effect of β-glucan, because both inhibition of microglia and their depletion prevented the antidepressant-like effect of β-glucan. Based on these effects of β-glucan, β-glucan administration could be developed as a new strategy for the treatment of depression.