Abstract
Proteo-β-glucan from Maitake (PGM) is a strong immune regulator, and its receptor is called Dectin-1. Cumulative evidence suggests that AMPA receptors are important for the treatment of depression. Here, we report that PGM treatment leads to a significant antidepressant effect in the tail suspension test and forced swim test after sixty minutes of treatment in mice. After five consecutive days of PGM treatment, this antidepressant effect remained. PGM treatment did not show a hyperactive effect in the open field test. PGM significantly enhanced the expression of its receptor Dectin-1, as well as p-GluA1(S845) and GluA1, but not GluA2 or GluA3 in the prefrontal cortex (PFC) after five days of treatment. The Dectin-1 inhibitor Laminarin was able to block the antidepressant effect of PGM. At the synapses of PFC, PGM treatment significantly up-regulated the p-GluA1(S845), GluA1, GluA2, and GluA3 levels. Moreover, PGM’s antidepressant effects and the increase of p-GluA1(S845)/GluA1 lasted for 3 days after stopping treatment. The AMPA-specific antagonist GYKI 52466 was able to block the antidepressant effect of PGM. This study identified PGM as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signalling.
Highlights
Signalling to exert its antidepressant efficacy[1,10]
After 60 minutes of treatment with Proteo-β-glucan from Maitake (PGM), the data showed that the duration of immobility in the PGM-treated groups was significantly lower than that of the controls (103.8 ± 14.5 sec), as low as 51.0 ± 9.5 sec, 52.3 ± 10.0 sec, and 50.5 ± 9.1 sec for forced swim test (FST), similar to the traditional antidepressant imipramine (51.5 ± 12.2 sec) (ANOVA, F(4,54) = 4.348, p < 0.01) (Fig. 2B)
The Dectin-1/AMPA receptor signalling pathway demonstrated a novel mechanism that is closely related to the neuroimmune system
Summary
Signalling to exert its antidepressant efficacy[1,10]. The AMPA receptor has emerged as a central mediator for the pathophysiology and treatment of depression[11,12,13]. The AMPA receptor potentiator (LY392098) had an antidepressant effect in animal models[17]. Increasing evidence suggests that AMPA receptors serve as central mediators during the development of the pathophysiology and treatment of depression[16]. Whether PGM regulates AMPA synaptic plasticity is still unknown In this context, we designed a series of behavioural and biochemical experiments to investigate the antidepressant effects of PGM in the animal models of depression. We first studied the effects of various concentrations of PGM on animal models of depression. The phosphorylation of AMPA GluA1 S845 and the expression of AMPA GluA1, GluA2, and GluA3 were studied in the total protein extract and in the synaptic fraction of the prefrontal cortex (PFC) after PGM treatment. The role of the enhanced AMPA function in the antidepressant effect of PGM was addressed by treatment with an AMPA-specific antagonist, GYKI 52466
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