黄酮类化合物对和脑健康.ppt

* * * * * * * * * * * * * * * * Changes in Hippocampal ERK1/2 pERK 44 pERK 42 Y Y O B O B ERK2 pERK 44 pERK 42 a *** b ** Relative Band Intensity pERK/ERK 0.0 0.5 1.0 1.5 2.0 Aged Young Aged + BB a/b = p ? 0.001 *** = p ? 0.001 ** = p ? 0.01 ERK PKC CREB PKA CaMK Hippocampal changes in Akt pAkt (Ser 473) Akt PKA C CaMKIV (Thr 196) CaMKIV Y Y O B O B pAkt (Ser 473) CaMKIV (Thr 196) PKA (Thr 197) *** b Relative Band Intensity 0.0 0.5 1.0 1.5 2.0 a a Aged Young Aged + BB a/b = p ? 0.001 *** = p ? 0.001 PI3K TrkB Akt BDNF Enhancement of Hippocampal Protein Synthesis ERK PI3K TrkB mTOR Homer2 Arc/Arg3.1 Akt BDNF mTOR (Ser 2448) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 *** a Relative Band Intensity Phospho-mTOR/ Total mTOR mTOR (Ser 2481) Arc/Arg3.1 NR4A2 0.0 0.5 1.0 1.5 2.0 2.5 Band Intensity *** a Aged Young Aged + BB ERK PKC CREB PI3K BDNF TrkB mTOR Homer2 Postsynaptic NMDA-R PKA CaMK Arc/Arg3.1 Akt BDNF ‘Enhancement of Protein Synthesis’ Presynaptic ‘Glutamate Release’ AMPA-R (1) (2) (3) Proposed mechanism of action I Spencer et al: Chem Soc Rev, 2009 Postsynaptic Presynaptic TrkB NMDA-R AMPA-R ‘Increased Synaptic Receptor Density’ ‘Dendritic spinal growth’ - mushroom spines Synapse following LTP ERK PI3K mTOR Homer2 Arc/Arg3.1 Akt ‘Glutamate Release’ ‘F-actin 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 communication (synaptic plasticity) Plant Bioactives Cell Signalling and Gene Expression Vascular Effects Neuronal Morphology * Flavonoids improve Peripheral and Cerebral Blood Flow Nitric oxide-dependent 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, 2003 Neurogenesis? * Neurogenesis * The Future: Brain Imaging, morphology and Networks * Summary Flavonoid-rich diet