5-HTT independent effects of fluoxetine on neuroplasticity
| Autor: | Corinne Poilbout, Gunter Kenis, Marion J. F. Levy, F. Boulle, Laurence Lanfumey, Harry W.M. Steinbusch, Daniel L.A. van den Hove, M. B. Emerit |
|---|---|
| Přispěvatelé: | Academic Affairs, Faculteit FHML Centraal, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Niet Med Staf Psychiatrie (9) |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Tropomyosin receptor kinase B Hippocampus ACTIVATION Mice 0302 clinical medicine SYNAPTIC PLASTICITY Neurotrophic factors TYROSINE KINASE-B lcsh:Science Receptor Serotonin transporter GENE-EXPRESSION Mice Knockout Serotonin Plasma Membrane Transport Proteins Membrane Glycoproteins Neuronal Plasticity Multidisciplinary biology Depression Kinase Chemistry MOUSE MODEL Protein-Tyrosine Kinases ANTIDEPRESSANT DRUGS MESSENGER-RNA Signal Transduction medicine.drug medicine.medical_specialty Article 03 medical and health sciences Fluoxetine Internal medicine Neuroplasticity medicine Animals RECEPTOR Brain-Derived Neurotrophic Factor lcsh:R 030104 developmental biology Endocrinology POSTMORTEM BRAIN nervous system Synaptic plasticity biology.protein lcsh:Q 030217 neurology & neurosurgery NEUROTROPHIC FACTOR |
| Zdroj: | Scientific Reports, 9:6311. Nature Publishing Group Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Selective serotonin reuptake inhibitors are among the most prescribed antidepressants. Fluoxetine is the lead molecule which exerts its therapeutic effects, at least in part, by promoting neuroplasticity through increased brain-derived neurotrophic factor (BDNF)/tropomyosin-related receptor kinase B (TrkB) signalling. It is unclear however, to which extent the neuroplastic effects of fluoxetine are solely mediated by the inhibition of the serotonin transporter (5-HTT). To answer this question, the effects of fluoxetine on neuroplasticity were analysed in both wild type (WT) and 5-Htt knock-out (KO) mice. Using Western blotting and RT-qPCR approaches, we showed that fluoxetine 10 µM activated BDNF/TrkB signalling pathways in both CD1 and C57BL/6J mouse primary cortical neurons. Interestingly, effects on BDNF signalling were observed in primary cortical neurons from both 5-Htt WT and KO mice. In addition, a 3-week in vivo fluoxetine treatment (15 mg/kg/d; i.p.) increased the expression of plasticity genes in brains of both 5-Htt WT and KO mice, and tended to equally enhance hippocampal cell proliferation in both genotypes, without reaching significance. Our results further suggest that fluoxetine-induced neuroplasticity does not solely depend on 5-HTT blockade, but might rely, at least in part, on 5-HTT-independent direct activation of TrkB. |
| Databáze: | OpenAIRE |
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