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The antidepressant hyperforin increases the phosphorylation of CREB and the expression of TrkB in a tissue-specific manner.
Gibon J., Deloulme J.-C., Chevallier T., Ladevèze E., Abrous D. N., Bouron A.
International Journal of Neuropsychopharmacology 16, 1 (2012) 189-98 - http://www.hal.inserm.fr/inserm-00739720
The antidepressant hyperforin increases the phosphorylation of CREB and the expression of TrkB in a tissue-specific manner.
Julien Gibon1, Jean-Christophe Deloulme2, Tiphaine Chevallier3, Elodie Ladevèze3, Djoher Nora Abrous3, Alexandre Bouron () 1
1 :  LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
CNRS : UMR5249 – CEA : DSV/IRTSV – Université Joseph Fourier - Grenoble I
17, rue des Martyrs 38054 GRENOBLE CEDEX 9
2 :  GIN - U836 - Grenoble Institut des Neurosciences
INSERM : U836 – Université Joseph Fourier - Grenoble I – CHU Grenoble – CEA : DSV/IRTSV
UJF - Site Santé La Tronche - BP 170 - 38042 Grenoble Cedex 9
3 :  Physiopathologie du système nerveux central - Institut François Magendie
INSERM : U862 – IFR8 – Université Victor Segalen - Bordeaux II
Institut Francois Magendie 146, rue leo saignat 33077 BORDEAUX CEDEX
INSERM U836, équipe 1, Physiopathologie du cytosquelette
Hyperforin is one of the main bioactive compounds that underlie the antidepressant actions of the medicinal plant Hypericum perforatum (St. John's wort). However, the effects of a chronic hyperforin treatment on brain cells remains to be fully addressed. The following study was undertaken to further advance our understanding of the biological effects of this plant extract on neurons. Special attention was given to its impact on the brain-derived neurotrophic factor (BDNF) receptor TrkB and on adult hippocampal neurogenesis since they appear central to the mechanisms of action of antidepressants. The consequences of a chronic hyperforin treatment were investigated on cortical neurons in culture and on the brain of adult mice treated for 4 wk with a daily injection (i.p.) of hyperforin (4 mg/kg). Its effects on the expression of the cyclic adenosine monophosphate response element-binding protein (CREB), phospho-CREB (p-CREB), TrkB and phospho-TrkB (p-TrkB) were analysed by Western blot experiments and its impact on adult hippocampal neurogenesis was also investigated. Hyperforin stimulated the expression of TRPC6 channels and TrkB via SKF-96365-sensitive channels controlling a downstream signalling cascade involving Ca2+, protein kinase A, CREB and p-CREB. In vivo, hyperforin augmented the expression of TrkB in the cortex but not in the hippocampus where hippocampal neurogenesis remained unchanged. In conclusion, this plant extract acts on the cortical BDNF/TrkB pathway leaving adult hippocampal neurogenesis unaffected. This study provides new insights on the neuronal responses controlled by hyperforin. We propose that the cortex is an important brain structure targeted by hyperforin.
Sciences du Vivant/Biologie cellulaire
Sciences du Vivant/Neurosciences

Articles dans des revues avec comité de lecture
International Journal of Neuropsychopharmacology (Int J Neuropsychopharmacol)
Publisher Cambridge University Press (CUP)
ISSN 1461-1457 (eISSN : 1469-5111)

Antidepressants – CREB – neurogenesis – PKA – TrkB – TRPC6
MENRT; Région Rhône-Alpes (Cluster 11, "Handicap, Vieillissement, Neurosciences"); INSERM
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