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A critical role of mitochondria in BDNF-associated synaptic plasticity after one-week vortioxetine treatment
- Source :
- Chen, F, Danladi, J, Ardalan, M, Elfving, B, Müller, H K, Wegener, G, Sanchez, C & Nyengaard, J R 2018, ' A critical role of mitochondria in BDNF-associated synaptic plasticity after one-week vortioxetine treatment ', International Journal of Neuropsychopharmacology, vol. 21, no. 6, pp. 603-615 . https://doi.org/10.1093/ijnp/pyy022, International Journal of Neuropsychopharmacology
- Publication Year :
- 2018
-
Abstract
- Background 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 receptors.
- Subjects :
- Dynamins
Male
rac1 GTP-Binding Protein
0301 basic medicine
medicine.medical_specialty
Gene Expression
Biology
vortioxetine
Regular Research Articles
Rats, Sprague-Dawley
Synapse
03 medical and health sciences
0302 clinical medicine
synapse
Neurotrophic factors
Fluoxetine
Internal medicine
Gene expression
medicine
Animals
Pharmacology (medical)
RNA, Messenger
CA1 Region, Hippocampal
5-HT receptor
Pharmacology
Vortioxetine
Neuronal Plasticity
Depression
Brain-Derived Neurotrophic Factor
Antidepressive Agents
Mitochondria
Psychiatry and Mental health
BDNF
030104 developmental biology
Endocrinology
nervous system
depression
Dentate Gyrus
Synapses
Synaptic plasticity
Antidepressant
Proto-Oncogene Proteins c-fos
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Chen, F, Danladi, J, Ardalan, M, Elfving, B, Müller, H K, Wegener, G, Sanchez, C & Nyengaard, J R 2018, ' A critical role of mitochondria in BDNF-associated synaptic plasticity after one-week vortioxetine treatment ', International Journal of Neuropsychopharmacology, vol. 21, no. 6, pp. 603-615 . https://doi.org/10.1093/ijnp/pyy022, International Journal of Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....e570e5c8a6cb27a0f07e7551097f3315