title: Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channels.
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 Ca(2+) -permeable, resulting in intracellular Ca(2+) elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca(2+) 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 Ca(2+) transients and depolarizing inward currents sensitive to the TRPC channel blocker La(3+) , 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.
authors: Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. leuner@em.uni-frankfurt.de
authors: Kristina
authors: K
authors: Leuner
authors: Wei
authors: W
authors: Li
authors: Michelle D
authors: MD
authors: Amaral
authors: Stephanie
authors: S
authors: Rudolph
authors: Gaston
authors: G
authors: Calfa
authors: Anita M
authors: AM
authors: Schuwald
authors: Christian
authors: C
authors: Harteneck
authors: Takafumi
authors: T
authors: Inoue
authors: Lucas
authors: L
authors: Pozzo-Miller
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020902:Hypericum / Q000737:chemistry*; D007811:Lanthanum / Q000494:pharmacology; D009924:Organ Culture Techniques; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050052:TRPC Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology*; D014162:Transfection
chemical_list: D002121:Calcium Channel Blockers; D010936:Plant Extracts; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; D013729:Terpenes; C492145:Trpc6 protein, rat; D007811:Lanthanum; D010696:Phloroglucinol; C001654:hyperforin; D002118:Calcium