EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease Flaubert Tchantchou * , Yanan Xu * , Yanjue Wu * , Yves Christen † and Yuan Luo * ,‡ ,1 * Department of Pharmaceutical Sciences, School of Pharmacy, ‡ Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA; and † Ipsen, Paris, France 1 Correspondence: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA. E-mail: yluo@rx.umaryland.edu Standardized Ginkgo biloba extract EGb 761 exhibits beneficial effects to patients with Alzheimer’s disease (AD). It was previously demonstrated that EGb 761 inhibits amyloid beta (Aß) oligomerization in vitro , protects neuronal cells against Aß toxicity, and improves cognitive defects in a mouse model of AD (Tg 2576). In this study, the neurogenic potential of EGb 761 and its effect on cAMP response element binding protein (CREB) were examined in a double transgenic mouse model (TgAPP/PS1). EGb 761 significantly increases cell proliferation in the hippocampus of both young (6 months) and old (22 months) TgAPP/PS1 mice, and the total number of neuronal precursor cells in vitro in a dose-dependent manner. Furthermore, Aß oligomers inhibit phosphorylation of CREB and cell proliferation in the hippocampus of TgAPP/PS1 mice. Administration of EGb 761 reduces Aß oligomers and restores CREB phosphorylation in the hippocampus of these mice. The present findings suggest that 1) enhanced neurogenesis by EGb 761 may be mediated by activation of CREB, 2) stimulation of neurogenesis by EGb 761 may contribute to its beneficial effects in AD patients and improved cognitive functions in the mouse model of AD, and 3) EGb 761 has therapeutic potential for the prevention and improved treatment of AD.—Tchantchou, F., Xu, Y., Wu, Y., Christen, Y., Luo, Y. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease. Key Words: AD • dementia • neuronal cells • memory
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EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimers disease
Tchantchou, Flaubert; Xu, Yanan; Wu, Yanjue; Christen, Yves; Luo, Yuan
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, Volume 21 (10): 2400
Fed of American Socs for Experimental Biology – Aug 1, 2007
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