Hyperforin Modulates Dendritic Spine Morphology in Hippocampal Pyramidal Neurons by Activating Ca2-Permeable TRPC6 Channels

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

HIPPOCAMPUS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2013 p. 40 - 52

1050-9631

The standardized extract of the St. Johns 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 Ca2-permeable, resulting in intracellular Ca2 elevations. Indeed, hyperforinactivates TRPC6-mediated currents and Ca 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 Ca2 transients and depolarizinginward currents sensitive to the TRPC channel blocker La31, thus resemblingthe actions of the neurotrophin brain-derived neurotrophic factor(BDNF) in hippocampal pyramidal neurons. These results suggest thatthe antidepressant actions of St. Johns wort are mediated by a mechanismsimilar to that engaged by BDNF.