Lentinan produces a robust antidepressant-like effect via enhancing the prefrontal Dectin-1/AMPA receptor signaling pathway.
Lentinan (LNT) is an immune regulator and its potential and mechanism for the treatment of mood disorder is of our interest. Dectin-1 is a β-glucan (including LNT) receptor that regulates immune functions in many immune cell types. Cumulative evidence has suggested that the glutamatergic system seems to play an important role in the treatment of depression. Here, we studied the antidepressant-like effects of LNT and its therapeutical target in regulating the functions of AMPA receptors. We found that 60min treatment with LNT leads to a significant antidepressant-like effect in the tail suspension test (TST) and the forced swim test (FST) in mice. The antidepressant-like effects of LNT in TST and FST remained after 1day or 5days of injections. Additionally, LNT did not show a hyperactive effect in the open field test. Dectin-1 receptor levels were increased after LNT treatment for 5days and the specific Dectin-1 inhibitor laminarin was able to block the antidepressant-like effects of LNT. After 5days of treatment, LNT enhanced p-GluR1 (S845) in the prefrontal cortex (PFC); however, the total GluR1, GluR2, and GluR3 expression levels remained unchanged. We also found that the AMPA-specific blocker GYKI 52466 was able to block the antidepressant-like effects of LNT. This study identified LNT as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signaling.
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Hongkun
H
Bao
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Lijuan
L
Sun
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Life Sciences, Yunnan University, Kunming, Yunnan, PR China.
Ying
Y
Zhu
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Pengzhan
P
Ran
School of Life Sciences, Yunnan University, Kunming, Yunnan, PR China.
Weihong
W
Hu
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Keming
K
Zhu
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Bai
B
Li
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Yangyang
Y
Hou
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Jun
J
Nie
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Tangxin
T
Gao
Beijing Gragen Biotechnology Co. Ltd., Beijing, PR China.
Liping
L
Shan
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, PR China.
Kai
K
Du
School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Shangyong
S
Zheng
School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Bingrong
B
Zheng
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China.
Chunjie
C
Xiao
State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming, Yunnan, PR China; School of Medicine, Yunnan University,Kunming, Yunnan, PR China. Electronic address: dujing@ynu.edu.cn.
Jing
J
Du
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic; D001569:Benzodiazepines / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D019417:Hindlimb Suspension; D007099:Imipramine / Q000494:pharmacology; D037181:Lectins, C-Type / Q000378:metabolism*; D007912:Lentinan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D017397:Prefrontal Cortex / Q000187:drug effects*; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D000099181:Dectin-1
D000276:Adjuvants, Immunologic; D000929:Antidepressive Agents, Tricyclic; D001569:Benzodiazepines; D018691:Excitatory Amino Acid Antagonists; D007099:Imipramine; D037181:Lectins, C-Type; D007912:Lentinan; D018091:Receptors, AMPA; D051195:Toll-Like Receptor 2; D000099181:Dectin-1; C493486:Tlr2 protein, mouse; C061950:GYKI 52466
AMPA receptor; Animal behavior; Antidepressant; Dectin-1; GluR1; Lentinan