title: 7,8-Dihydroxyflavone reverses the depressive symptoms in mouse chronic mild stress.
abstract: 7,8-Dihydroxyflavone (7,8-DHF) is a naturally-occurring flavone which possesses good bioavailability. Due to its ability to cross the blood-brain barrier, previous studies have demonstrated that 7,8-DHF was a potent tropomyosin-related kinase B (TrkB) agonist, and produced antidepressant-like effects in mouse forced swimming test and tail suspension test. However, it has not been evaluated in chronic mild stress (CMS), a classical depression model modulating the processes of major depression in human. In the present study, we not only evaluated the depressive-like behaviors, but also measured the key proteins of TrkB signaling in mice exposed to CMS. Our results firstly found that long term but not single injection of 7,8-DHF restored the depressive-like behaviors in sucrose preference test and novelty suppressed feeding test. In addition, 7,8-DHF not only increased TrkB phosphorylation and brain-derived neurotrophic factor (BDNF) levels, but also activated the expression of TrkB downstream synaptic proteins such as PSD95 and synaptophysin. Furthermore, the TrkB antagonist K252a blocked the antidepressant-like effects of 7,8-DHF. In summary, the present results demonstrated that chronic 7,8-DHF treatment exerted significant antidepressant-like effects, which were likely attributed to regulating TrkB signaling and thus promoting synaptic protein expression.
authors: Department of Encephalopathy (II), Zhengzhou Traditional Chinese Medicine Hospital, Zhengzhou 450007, Henan province, PR China.
authors: Min-Wang
authors: MW
authors: Zhang
authors: Henan Province Chinese medicine research institute, Zhengzhou 450004, Henan province, PR China.
authors: She-Feng
authors: SF
authors: Zhang
authors: Department of Encephalopathy (II), Zhengzhou Traditional Chinese Medicine Hospital, Zhengzhou 450007, Henan province, PR China.
authors: Zhen-Hua
authors: ZH
authors: Li
authors: Department of Encephalopathy (II), Zhengzhou Traditional Chinese Medicine Hospital, Zhengzhou 450007, Henan province, PR China. Electronic address: zhangmw1981@163.com.
authors: Fang
authors: F
authors: Han
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D000076122:Disks Large Homolog 4 Protein; D047309:Flavones / Q000627:therapeutic use*; D005518:Food Preferences; D051528:Guanylate Kinases / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000188:drug therapy* / Q000523:psychology; D013395:Sucrose / Q000008:administration & dosage; D016708:Synaptophysin / Q000378:metabolism
chemical_list: C485383:6,7-dihydroxyflavone; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047309:Flavones; D026121:Indole Alkaloids; D008565:Membrane Proteins; D016708:Synaptophysin; D013395:Sucrose; C049985:staurosporine aglycone; D011505:Protein-Tyrosine Kinases; D051528:Guanylate Kinases
keywords: 7,8-Dihydroxyflavone (7,8-DHF); Antidepressant-like effects; Chronic mild stress (CMS); PSD95; Synaptophysin; TrkB