期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep36705
关键词
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资金
- Japan Society for Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and development, AMED
- Smoking Research Foundation, Tokyo, Japan
- Ishidsu Shun Memorial Scholarship (Tokyo, Japan)
- Research Fellowship for Young Scientists of the Japan Society for the Promotion of Science
- Uehara Memorial Foundation (Tokyo, Japan)
- Leading Graduate School at Chiba University
- Grants-in-Aid for Scientific Research [15K19711] Funding Source: KAKEN
The alpha 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 alpha 7 nAChR in depression using alpha 7 nAChR knock-out (KO) mice. Serum levels of tumor necrosis factor-a and interlukin-1 beta in KO mice were higher than wild-type mice, suggesting an inflammatory process in KO mice. alpha 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 alpha 7 nAChR plays a key role in depression.
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