Hyperforin Modulates Dendritic Spine Morphology in Hippocampal Pyramidal Neurons by Activating Ca21-Permeable TRPC6 Channels

LEUNER K, LI W, AMARAL M, RUDOLPH S, CALFA G, SCHUWALD AM, HARTENECK C, INOUE T, POZZO-MILLER L

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2013 p. 40 - 40

BSTRACT: The standardized extract of the St. John’s wort plant(Hypericum perforatum) is commonly used to treat mild to moderatedepression. Its active constituent is hyperforin, a phloroglucinol derivativethat reduces the reuptake of serotonin and norepinephrine byincreasing intracellular Na1 concentration through the activation ofnonselective cationic TRPC6 channels. TRPC6 channels are also Ca21-permeable, resulting in intracellular Ca21 elevations. Indeed, hyperforinactivates TRPC6-mediated currents and Ca21 transients in rat PC12cells, which induce their differentiation, mimicking the neurotrophiceffect of nerve growth factor. Here, we show that hyperforin modulatesdendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampalslice cultures through the activation of TRPC6 channels.Hyperforin also evoked intracellular Ca21 transients and depolarizinginward currents sensitive to the TRPC channel