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Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating $Ca^{2+}$-permeable TRPC6 channels
| Content Provider | Scilit |
|---|---|
| Author | Leuner, Kristina Li, Wei Amaral, Michelle D. Rudolph, Stephanie Calfa, Gaston Schuwald, Anita M. Harteneck, Christian Inoue, Takafumi Pozzo-Miller, Lucas |
| Copyright Year | 2012 |
| Description | Journal: Hippocampus 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538039/pdf |
| Ending Page | 52 |
| Page Count | 13 |
| Starting Page | 40 |
| ISSN | 10509631 |
| e-ISSN | 10981063 |
| DOI | 10.1002/hipo.22052 |
| Journal | Hippocampus |
| Issue Number | 1 |
| Volume Number | 23 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2012-07-20 |
| Access Restriction | Open |
| Subject Keyword | Journal: Hippocampus Ca1 Pyramidal Neuron Ca3 Pyramidal Neuron Biolistic Transfection Confocal Microscopy Organotypic Slice Culture Sirna‐mediated Knockdown |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cognitive Neuroscience |
