PMID- 22815087
OWN - NLM
STAT- MEDLINE
DCOM- 20130522
LR  - 20240318
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Print)
IS  - 1050-9631 (Linking)
VI  - 23
IP  - 1
DP  - 2013 Jan
TI  - Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons 
      by activating Ca(2+) -permeable TRPC6 channels.
PG  - 40-52
LID - 10.1002/hipo.22052 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Leuner, Kristina
AU  - Leuner K
AD  - Department of Neurobiology, Civitan International Research Center, The University 
      of Alabama at Birmingham, Birmingham, Alabama 35294, USA. 
      leuner@em.uni-frankfurt.de
FAU - Li, Wei
AU  - Li W
FAU - Amaral, Michelle D
AU  - Amaral MD
FAU - Rudolph, Stephanie
AU  - Rudolph S
FAU - Calfa, Gaston
AU  - Calfa G
FAU - Schuwald, Anita M
AU  - Schuwald AM
FAU - Harteneck, Christian
AU  - Harteneck C
FAU - Inoue, Takafumi
AU  - Inoue T
FAU - Pozzo-Miller, Lucas
AU  - Pozzo-Miller L
LA  - eng
GR  - P30 NS047466/NS/NINDS NIH HHS/United States
GR  - P30 HD038985/HD/NICHD NIH HHS/United States
GR  - R01 NS040593/NS/NINDS NIH HHS/United States
GR  - R01 NS065027/NS/NINDS NIH HHS/United States
GR  - P01 HD038760/HD/NICHD NIH HHS/United States
GR  - NS-065027/NS/NINDS NIH HHS/United States
GR  - NS40593/NS/NINDS NIH HHS/United States
GR  - R21 HD074418/HD/NICHD NIH HHS/United States
GR  - P30 NS057098/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120720
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Plant Extracts)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Terpenes)
RN  - 0 (Trpc6 protein, rat)
RN  - 6I3K30563S (Lanthanum)
RN  - DHD7FFG6YS (Phloroglucinol)
RN  - RM741E34FP (hyperforin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Dendritic Spines/*drug effects/metabolism
MH  - Depression/drug therapy/metabolism
MH  - Gene Expression/physiology
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Hypericum/*chemistry
MH  - Lanthanum/pharmacology
MH  - Organ Culture Techniques
MH  - Phloroglucinol/*analogs & derivatives/pharmacology
MH  - Plant Extracts/*pharmacology
MH  - Pyramidal Cells/*drug effects/metabolism/ultrastructure
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TRPC Cation Channels/*agonists/antagonists & inhibitors/genetics
MH  - Terpenes/*pharmacology
MH  - Transfection
PMC - PMC3538039
MID - NIHMS388431
EDAT- 2012/07/21 06:00
MHDA- 2013/05/23 06:00
PMCR- 2014/01/01
CRDT- 2012/07/21 06:00
PHST- 2012/06/19 00:00 [accepted]
PHST- 2012/07/21 06:00 [entrez]
PHST- 2012/07/21 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.1002/hipo.22052 [doi]
PST - ppublish
SO  - Hippocampus. 2013 Jan;23(1):40-52. doi: 10.1002/hipo.22052. Epub 2012 Jul 20.