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. beta-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 beta-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 beta-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 beta-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 beta-glucan injection, no antidepressant-like effect was observed anymore. However, this effect was overcome by a second beta-glucan injection (20 mg/kg) 14 days after the first beta-glucan injection. Stimulation of microglia appeared to mediate the antidepressant-like effect of beta-glucan, because both inhibition of microglia and their depletion prevented the antidepressant-like effect of beta-glucan. Based on these effects of beta-glucan, beta-glucan administration could be developed as a new strategy for the treatment of depression.

Automated summary

The decline of microglia in the hippocampus has been linked to the development of depression, and the reversal of this decline shows antidepressant effects. Beta-glucan, a polysaccharide, has beneficial effects on the nervous system and may correct the functional deficiency of microglia. In animal studies, beta-glucan administration reversed depression-like behaviors induced by chronic stress and its effects were mediated by microglia stimulation.