Journal
NEUROPHARMACOLOGY
Volume 58, Issue 6, Pages 911-920Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.11.002
Keywords
Depression; Neuroplasticity; Amyloid beta oligomers; Natural flavonoids
Categories
Funding
- NIH, National Center for Complementary and Alternative Medicine [RO1AT001928-03A1]
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Increasing evidence suggests that depression may be both a cause and consequence of neurological disorders such as Alzheimer's disease (AD), and that anti-depressants could provide an alternative strategy to current AD therapies. Association of side effect and herbal drug interaction with conventional anti-depressant and St. John's wort warrant investigating new anti-depressant drugs. Antidepressant effects of ginkgo biloba extract (EGb 761) have been demonstrated in animal models of depression and in human volunteers. We report here that ginkgo flavonols quercetin and kaempferol stimulates depression-related signaling pathways involving brain-derived neurotrophic factor BDNF/phosphorylation of cyclic AMP response element binding protein CREB/postsynaptic density proteins PSD95, and reduces amyloid-beta peptide (A beta) in neurons isolated from double transgenic AD mouse (TgAPPswe/PS1e9). In addition, enhanced BDNF expression and reduction of A beta oligomers was confirmed in hippocampus of the double transgenic mice administered with flavonol, which correlates with cognitive improvement behaviors in these mice. The present results suggest that stimulating BDNF and reducing A beta toxicity by natural flavonols provide a therapeutic implication for treatment of AD. (C) 2009 Elsevier Ltd. All rights reserved.
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