BDNF downregulates 5-HT2A receptor protein levels in hippocampal cultures

V. Trajkovska, M. A. Santini, A. B. Marcussen, M. S. Thomsen, H. H. Hansen, J. D. Mikkelsen, L. Arneberg, Merab Kokaia, G. M. Knudsen, S. Aznar

    Research output: Contribution to journalArticlepeer-review

    24 Citations (SciVal)

    Abstract

    Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT2A) have been related to depression pathology. Specific 5-HT2A receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT2A receptor level. Here we show a direct effect of BDNF on 5-HT2A receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT2A receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50 ng/mL BDNF resulted in downregulation of 5-HT2A, but not of 5-HT1A, receptor protein levels. The BDNF-associated downregulation of 5-HT2A receptor levels was also observed in mature hippocampal organotypic cultures, excluding confounding effects of BDNF on immature tissue. BDNF +/- mice showed significant increased 5-HT2A receptor levels in hippocampus confirming the association between 5-HT2A receptor and BDNF levels in vivo. In conclusion, our results point to a regulatory role of BDNF on 5-HT2A receptor levels. This interaction may be an important mechanism in the role of BDNF in affective disorders emphasizing the need for further elucidating the specificity and the mechanism behind this regulation. (C) 2009 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)697-702
    JournalNeurochemistry International
    Volume55
    Issue number7
    DOIs
    Publication statusPublished - 2009

    Bibliographical note

    The information about affiliations in this record was updated in December 2015.
    The record was previously connected to the following departments: Restorative Neurology (0131000160)

    Subject classification (UKÄ)

    • Neurosciences

    Keywords

    • Hippocampus
    • Mature organotypic cultures
    • Serotonin
    • Neurotrophins
    • Depression
    • Neuronal cultures

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