| First Author | Zhang JC | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 36705 | PubMed ID | 27821848 |
| Mgi Jnum | J:328399 | Mgi Id | MGI:6224788 |
| Doi | 10.1038/srep36705 | Citation | Zhang JC, et al. (2016) Depression-like phenotype by deletion of alpha7 nicotinic acetylcholine receptor: Role of BDNF-TrkB in nucleus accumbens. Sci Rep 6:36705 |
| abstractText | The alpha7 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 alpha7 nAChR in depression using alpha7 nAChR knock-out (KO) mice. Serum levels of tumor necrosis factor-alpha and interlukin-1beta in KO mice were higher than wild-type mice, suggesting an inflammatory process in KO mice. alpha7 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 alpha7 nAChR plays a key role in depression. |
