The antidepressant hyperforin increases the phosphorylation of CREB and the expression of TrkB in a tissue-specific manner.
Int. J. Neuropsychopharm.. 2012-01-09; 16(01): 189-198
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1. Int J Neuropsychopharmacol. 2013 Feb;16(1):189-98. doi:
10.1017/S146114571100188X. Epub 2012 Jan 9.
The antidepressant hyperforin increases the phosphorylation of CREB and the
expression of TrkB in a tissue-specific manner.
Gibon J(1), Deloulme JC, Chevallier T, Ladevèze E, Abrous DN, Bouron A.
(1)UMR CNRS 5249, Grenoble, France.
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 Ca(2+), 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.
PMID: 22226089 [Indexed for MEDLINE]