title: Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons.
abstract: Loss of synapses has been correlated with dementia in Alzheimer's disease (AD) as an early event during the disease progression. Hence, synaptogenesis and neurogenesis in adulthood could serve as a therapeutic target for the prevention and treatment of AD. Recently, we have demonstrated enhanced hippocampal neurogenesis by oral administration of Ginkgo biloba extract (EGb 761) to a mouse model of AD. This study aims to identify the constituents that contribute to EGb 761-induced neurogenesis. Among the constituents tested, bilobalide and quercetin significantly increased cell proliferation in the hippocampal neurons in a dose-dependent manner. Bilobalide and quercetin also enhanced phosphorylation of cyclic-AMP Response Element Binding Protein (CREB) in these cells, and elevated the levels of pCREB and, brain-derived neurotrophic factor in mice brain. Immunofluorescence staining of synaptic markers shows remarkable dendritic processes in hippocampal neurons treated with either quercetin or bilobalide. Furthermore, both constituents restored amyloid-beta oligomers (also known as ADDL)-induced synaptic loss and phosphorylation of CREB. The present findings suggest that enhanced neurogenesis and synaptogenesis by bilobalide and quercetin may share a common final signaling pathway mediated by phosphorylation of CREB. Despite a recent report showing that EGb 761 was insufficient in prevent dementia, its constituents still warrant future investigation.
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors: Flaubert
authors: F
authors: Tchantchou
authors: Pascale N
authors: PN
authors: Lacor
authors: Zhiming
authors: Z
authors: Cao
authors: Lixing
authors: L
authors: Lao
authors: Yan
authors: Y
authors: Hou
authors: Changhai
authors: C
authors: Cui
authors: William L
authors: WL
authors: Klein
authors: Yuan
authors: Y
authors: Luo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects; D000096983:Ginkgo Extract
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D003517:Cyclopentanes; D005663:Furans; D046934:Ginkgolides; D010936:Plant Extracts; D011794:Quercetin; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C073710:bilobalide