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Abstract (English)

Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT2A receptor expression. A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. In adult mice, intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings demonstrating the prevalence of 5-HT2A–TrkB heteroreceptor complexes in these brain regions. An expression analysis revealed strong developmental regulation of 5-HT2A and TrkB expressions in the cortex, hippocampus, and especially the striatum, demonstrating that the balance between TrkB and 5-HT2A may shift in certain brain regions during postnatal development. Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated expression of 5-HT2A and TrkB is a molecular mechanism for the brain-region-specific modulation of TrkB functions during development and under pathophysiological conditions.

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Cells, 11 (2022), 15, 2384. https://doi.org/10.3390/cells11152384. ISSN: 2073-4409
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English

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610 Medicine and health

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Sustainable Development Goals

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@article{Ilchibaeva2022, url = {https://hohpublica.uni-hohenheim.de/handle/123456789/16594}, doi = {10.3390/cells11152384}, author = {Ilchibaeva, Tatiana and Tsybko, Anton and Zeug, Andre et al.}, title = {Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes}, journal = {Cells}, year = {2022}, volume = {11}, number = {15}, }
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