Obligatory role of microglia-mobilized hippocampal CREB-BDNF signaling in the prophylactic effect of β-glucan on chronic stress-induced depression-like behaviors in mice

Eur J Pharmacol. 2023 Dec 22:176288. doi: 10.1016/j.ejphar.2023.176288. Online ahead of print.ABSTRACTOur previous studies have reported that pre-stimulation of microglia before stress stimulation is a possible strategy to prevent depression-like phenotypes; however, the molecular mechanisms underlying this effect are still unclear. Here, we used β-glucan, a polysaccharide from Saccharomyces cerevisiae with immunomodulatory activities that cannot elicit pro-inflammatory responses in microglia, to address this issue. Our results showed that a single injection of β-glucan one day before stress exposure dose-dependently prevented the depression-like behaviors triggered by chronic unpredictable stress (CUS), which peaked at 20 mg/kg and prevented the impairment of hippocampal brain-derived neurotrophic factor (BDNF) signaling, a pathological process critical for the progression of depression-like phenotypes. Inhibition of BDNF signaling by infusion of an anti-BDNF antibody into the hippocampus, knock-in of the mutant BDNF Val68Met allele, or blockade of the BDNF receptor in the hippocampus abolished the preventive effect of β-glucan on CUS-induced depression-like behaviors. Further analysis showed that cAMP-response element binding protein (CREB)-mediated increase of BDNF expression in the hippocampus was essential for the prevention of depression-like phenotypes by β-glucan. Pretreatment with minocycline or PLX3397 before β-glucan injection to suppress microglia abolished t...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research