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dc.contributor.authorChen, Fenghua
dc.contributor.authorWegener, Gregers
dc.contributor.authorDanladi, Jibrin
dc.contributor.authorArdalan, Maryam
dc.contributor.authorElfving, Betina
dc.date.accessioned2018-09-04T13:15:16Z
dc.date.available2018-09-04T13:15:16Z
dc.date.issued2018
dc.identifier.citationChen, F. et al. 2018. A critical role of mitochondria in BDNF-associated synaptic plasticity after one-week vortioxetine treatment. International journal of neuropsychopharmacology, 21(6):603-615. [https://doi.org/10.1093/ijnp/pyy022]en_US
dc.identifier.issn1461-1457
dc.identifier.issn1469-5111 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/30881
dc.identifier.urihttps://academic.oup.com/ijnp/article-pdf/21/6/603/24977718/pyy022.pdf
dc.identifier.urihttps://doi.org/10.1093/ijnp/pyy022
dc.description.abstractBackground Preclinical studies have indicated that antidepressant effect of vortioxetine involves increased synaptic plasticity and promotion of spine maturation. Mitochondria dysfunction may contribute to the pathophysiological basis of major depressive disorder. Taking into consideration that vortioxetine increases spine number and dendritic branching in hippocampus CA1 faster than fluoxetine, we hypothesize that new spines induced by vortioxetine can rapidly form functional synapses by mitochondrial support, accompanied by increased brain-derived neurotrophic factor signaling. Methods Rats were treated for 1 week with vortioxetine or fluoxetine at pharmacologically relevant doses. Number of synapses and mitochondria in hippocampus CA1 were quantified by electron microscopy. Brain-derived neurotrophic factor protein levels were visualized with immunohistochemistry. Gene and protein expression of synapse and mitochondria-related markers were investigated with real-time quantitative polymerase chain reaction and immunoblotting. Results Vortioxetine increased number of synapses and mitochondria significantly, whereas fluoxetine had no effect after 1-week dosing. BDNF levels in hippocampus DG and CA1 were significantly higher after vortioxetine treatment. Gene expression levels of Rac1 after vortioxetine treatment were significantly increased. There was a tendency towards increased gene expression levels of Drp1 and protein levels of Rac1. However, both gene and protein levels of c-Fos were significantly decreased. Furthermore, there was a significant positive correlation between BDNF levels and mitochondria and synapse numbers. Conclusion Our results imply that mitochondria play a critical role in synaptic plasticity accompanied by increased BDNF levels. Rapid changes in BDNF levels and synaptic/mitochondria plasticity of hippocampus following vortioxetine compared with fluoxetine may be ascribed to vortioxetine’s modulation of serotonin receptorsen_US
dc.language.isoenen_US
dc.publisherOxford Univ Pressen_US
dc.subjectSynapseen_US
dc.subjectMitochondriaen_US
dc.subjectBDNFen_US
dc.subjectDepressionen_US
dc.subjectVortioxetineen_US
dc.titleA critical role of mitochondria in BDNF-associated synaptic plasticity after one-week vortioxetine treatmenten_US
dc.typeArticleen_US
dc.contributor.researchID22353003 - Wegener, Gregers


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