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Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca2+-permeable TRPC6 channels

Authors

  • Kristina Leuner,

    Corresponding author
    1. Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294
    2. Department of Pharmacology, University of Frankfurt, Germany
    3. Molecular und Clinical Pharmacy, Friedrich-Alexander-University Erlangen/Nürnberg, Germany
    • Department of Pharmacology, University of Frankfurt, Max-von-Laue-Str.9, 60438 Frankfurt, Germany
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  • Wei Li,

    1. Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294
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  • Michelle D. Amaral,

    1. Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294
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  • Stephanie Rudolph,

    1. Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294
    2. Physiological Institute, University of Freiburg, Germany
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  • Gaston Calfa,

    1. Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294
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  • Anita M. Schuwald,

    1. Department of Pharmacology, University of Frankfurt, Germany
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  • Christian Harteneck,

    1. Institute of Pharmacology and Toxicology & Interfaculty Centre for Pharmacogenomics and Drug Research, Eberhard-Karls-University, Tübingen, Germany
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  • Takafumi Inoue,

    1. Department of Life Science and Medical Bioscience, Faculty of Science and Engineering, Waseda University, Tokyo 162-8480, Japan
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  • Lucas Pozzo-Miller

    1. Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294
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Abstract

The standardized extract of the St. John's wort plant (Hypericum perforatum) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na+ concentration through the activation of nonselective cationic TRPC6 channels. TRPC6 channels are also Ca2+-permeable, resulting in intracellular Ca2+ elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca2+ transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of nerve growth factor. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca2+ transients and depolarizing inward currents sensitive to the TRPC channel blocker La3+, thus resembling the actions of the neurotrophin brain-derived neurotrophic factor (BDNF) in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John's wort are mediated by a mechanism similar to that engaged by BDNF. © 2012 Wiley Periodicals, Inc.

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