Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1-42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus.
The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset of learning and memory deficits along with spontaneous overproduction of soluble beta-amyloid peptide (Abeta) in the brain. In our study, 4 month old male SAMP8 mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months. We found that a supplementation with 0.05% or 0.1% GTC prevented spatial learning and memory impairments of mice in the Morris water maze. Better performance of GTC-treated mice was associated with decreased levels of Abeta(1-42) oligomers in the hippocampus. The activity of the protein kinase A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular targets of Abeta oligomers which is crucial for late long-term potentiation and long-term memory formation, was significantly increased after GTC administration. We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions of three representative proteins of synaptic function and synaptic structure, including brain-derived neurotrophic factor(BDNF), post-synaptic density protein-95 (PSD95) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent spatial learning and memory decline of SAMP8 mice by decreasing Abeta(1-42) oligomers and upregulating synaptic plasticity-related proteins in the hippocampus.
Li
Q
Q
Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China.
Zhao
H F
HF
Zhang
Z F
ZF
Liu
Z G
ZG
Pei
X R
XR
Wang
J B
JB
Li
Y
Y
D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis*; D028241:Camellia sinensis; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007858:Learning / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008568:Memory / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D013037:Spatial Behavior / Q000187:drug effects*; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002392:Catechin; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D051528:Guanylate Kinases