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黃酮類化合物和腦健康-資料下載頁

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【正文】 B a/b = p ? *** = p ? PI3K TrkB Akt BDNF Enhancement of Hippocampal Protein Synthesis ERK PI3K TrkB mTOR Homer2 Arc/ Akt BDNF mTOR (Ser 2448) *** a Relative Band Intensity PhosphomTOR/ Total mTOR mTOR (Ser 2481) Arc/ NR4A2 Band Intensity *** a Aged Young Aged + BB ERK PKC CREB PI3K BDNF TrkB mTOR Homer2 Postsynaptic NMDAR PKA CaMK Arc/ Akt BDNF ‘Enhancement of Protein Synthesis’ Presynaptic ‘Glutamate Release’ AMPAR (1) (2) (3) Proposed mechanism of action I Spencer et al: Chem Soc Rev, 2022 Postsynaptic Presynaptic TrkB NMDAR AMPAR ‘Increased Synaptic Receptor Density’ ‘Dendritic spinal growth’ mushroom spines Synapse following LTP ERK PI3K mTOR Homer2 Arc/ Akt ‘Glutamate Release’ ‘Factin Expansion’ Cofilin ‘Sustained Activation of Arc, mTOR’ Proposed mechanism of action II Interactions with the architecture of memory and cognition New nerve cell growth (neurogenesis) Increased neuronal munication (synaptic plasticity) Plant Bioactives Cell Signalling and Gene Expression Vascular Effects Neuronal Morphology 37 Flavonoids improve Peripheral and Cerebral Blood Flow Nitric oxidedependent Vasodilatation Acute changes in brain blood flow Modulation of vascular signalling and factors linked with neurogenesis Acute improvements in vascular responsiveness Heiss et al. JAMA, 2022 Neurogenesis? 38 Neurogenesis 39 The Future: Brain Imaging, morphology and Networks 40 Summary ? Flavonoidrich diets are capable of reversing agerelated declines in spatial working memory. ? The effects of dietary flavonoids/metabolites are seemingly independent of their antioxidant potential. ? Flavonoids appear to induce cellular effects via specific interactions within cell signalling cascades, such as the MAP kinase pathway. ? The beneficial effects of flavonoids on the reversal of the ageassociated cognitive decline might be mediated through modifications of CREB and CREBdependant gene expression Acknowledgements Dr. Manal Abd El Mohsen Dr. Giulia Corona Dr. Ana RodriquezMateos Dr. MariaJose OrunaConcha Dr. Katerina Vafeiadou Dr. David Vauzour Prof. Judi Ellis Dr. Laurie Butler Dr. Claire Williams Vanessa Collins Geina Dodd Eva Hernandez Pauline How Susie Jennings Sara Neshatdoust Catarina Rendeiro Caroline Saunders Setarah Tabatabaee Xenofon Tzounis 43

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