title: The Prefrontal Dectin-1/AMPA Receptor Signaling Pathway Mediates The Robust and Prolonged Antidepressant Effect of Proteo-β-Glucan from Maitake.
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.
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Hongkun
authors.initials: H
authors.lastname: Bao
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Pengzhan
authors.initials: P
authors.lastname: Ran
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Bai
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Hou
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Nie
authors.affiliation: Beijing Gragen Biotechnology Co. Ltd., Beijing, P. R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Shan
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Shangyong
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P. R. China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Xiao
authors.affiliation: State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, P. R. China.|School of Medicine, Yunnan University, Kunming, Yunnan, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D048691:Grifola / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D051379:Mice; D010940:Plant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D047071:beta-Glucans / Q000008:administration & dosage* / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D000928:Antidepressive Agents; D001569:Benzodiazepines; D037181:Lectins, C-Type; D010940:Plant Proteins; D018091:Receptors, AMPA; D047071:beta-Glucans; D000099181:Dectin-1; C061950:GYKI 52466