Depression-like phenotype by deletion of ?7 nicotinic acetylcholine receptor: Role of BDNF-TrkB in nucleus accumbens.

ABSTRACT: The ?7 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 ?7 nAChR in depression using ?7 nAChR knock-out (KO) mice. Serum levels of tumor necrosis factor-? and interlukin-1? in KO mice were higher than wild-type mice, suggesting an inflammatory process in KO mice. ?7 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 ?7 nAChR plays a key role in depression.

SUBMITTER: Zhang JC 

PROVIDER: S-EPMC5099687 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature