文章基本信息

标题：Depression-like phenotype by deletion of α7 nicotinic acetylcholine receptor: Role of BDNF-TrkB in nucleus accumbens
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作者：Ji-chun Zhang ; Wei Yao ; Qian Ren 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep36705
语种：English
出版社：Springer Nature
摘要：The α7 subtype of nicotinic acetylcholine receptor (nAChR) plays a role in the inflammation which is implicated in depression. This study was undertaken to examine the role of α7 nAChR in depression using α7 nAChR knock-out (KO) mice. Serum levels of tumor necrosis factor-α and interlukin-1β in KO mice were higher than wild-type mice, suggesting an inflammatory process in KO mice. α7 nAChR KO mice showed depression-like phenotype. Furthermore, KO mice showed increased brain-derived neurotrophic factor (BDNF) and its receptor TrkB signaling, as well as increased synaptogenesis and spine density in the nucleus accumbens (NAc), although BDNF-TrkB signaling and synaptogenesis were not altered in the prefrontal cortex and hippocampus. Systemic administration of the TrkB antagonist ANA-12, but not the TrkB agonist 7,8-dihydroxyflavone and the selective serotonin reuptake inhibitor fluoxetine, showed a rapid antidepressant effect in KO mice by normalizing increased synaptogenesis in the NAc. In addition, bilateral infusion of ANA-12 into NAc promoted a rapid antidepressant effect in KO mice by normalizing increased synaptogenesis in the NAc. These findings suggest that increased BDNF-TrkB signaling and synaptogenesis in the NAc by deletion of α7 nAChR plays a key role in depression.