Your search for: 'author:("Lacor, Pascale N.")' has returned 2 results. (0.055s) Save search

Authors: Tchantchou, Flaubert | Lacor, Pascale N. | Cao, Zhiming | Lao, Lixing | Hou, Yan | Cui, Changhai | Klein, William L. | Luo, Yuan

Article Type: Research Article

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-β 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. Show more

Keywords: Amyloid-beta derived diffusible ligands (ADDL), bilobalide, CREB, neurogenesis, quercetin, synaptogenesis

DOI: 10.3233/JAD-2009-1189

Citation: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 787-798, 2009

Authors: Xiao, Chun | Davis, Francesca J. | Chauhan, Balwantsinh C. | Viola, Kirsten L. | Lacor, Pascale N. | Velasco, Pauline T. | Klein, William L. | Chauhan, Neelima B.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is a global health crisis with limited treatment options. Despite major advances in neurotherapeutics, poor brain penetration due to the blood-brain barrier continues to pose a big challenge in overcoming the access of therapeutics to the central nervous system. In that regard, the non-invasive intranasal route of brain targeting is gaining considerable attention. The nasal mucosa offers a large surface area, rapid absorption, and avoidance of first-pass metabolism increasing drug bioavailability with less systemic side effects. Intranasal delivery is known to utilize olfactory, rostral migratory stream, and trigeminal routes to reach the brain. This investigation confirmed that …intranasal delivery of oligomeric amyloid-β antibody (NU4) utilized all three routes to enter the brain with a resident time of 96 hours post single bolus intranasal administration, and showed evidence of perikaryal and parenchymal uptake of NU4 in 5XFAD mouse brain, confirming the intranasal route as a non-invasive and efficient way of delivering therapeutics to the brain. In addition, this study demonstrated that intranasal delivery of NU4 antibody lowered cerebral amyloid-β and improved spatial learning in 5XFAD mice. Show more

Keywords: Alzheimer's immunotherapy, amyloid-β oligomer antibody, brain transit, cerebral amyloid-β immunocytochemistry, intranasal delivery, olfactory pathway, rostral migratory stream pathway, spatial acquisition learning, trigeminal pathway

DOI: 10.3233/JAD-122419

Citation: Journal of Alzheimer's Disease, vol. 35, no. 4, pp. 777-788, 2013