Program

PO1-1-32

EPIGALLOGATECHIN-3-GALLATE IMPROVES COGNITIVE DECLINE AND METABOLIC ALTERATIONS IN APP/PS1 FAMILIAL MODEL OF ALZHEIMER'S DISEASE FED WITH HIGH FAT DIET

[Speaker] Miren Ettcheto:1,2,3,4
[Co-author] Amanda Cano:5,6, Oriol Busquets:1,2,3,4, Saghar Rabiei-Poor:1, Carme Auladell:2,3,7, Jaume Folch:2,4, Antoni Camins:1,2,3
1:Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Spain, 2:Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid., Spain, 3:Institute of Neuroscience, University of Barcelona, Spain, 4:Department of Biochemistry, Faculty of Medicine and Life Science, University of Rovira i Virgili, Reus., Spain, 5:Unit of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Spain, 6:Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Spain, 7:Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain

Alzheimer´s disease (AD) is the most common form of dementia, which is characterize by the presence of extracellular β amyloid plaques and intracellular neurofibrillary tangles. Although its etiology remains unclear, several studies point out that metabolic disorders such as Diabetes Mellitus type 2 could be one of the causes to develop sporadic AD. Moreover, it is known that epigallocatechin-3-gallate (EGCG), one of the major polyphenol of the green tea, has an important protective effect against neuronal damage turning into a potential drug for the treatment of AD. Thus, the aim of this study was to evaluate both, peripheral and central effects of EGCG in 6 month-old APP/PS1 familial AD mouse model exacerbated by the intake of high fat diet (HFD).
EGCG was administrated daily, in drinking water, at a dose of 40mg/kg in APP/PS1 fed with HFD and wild-type (WT) mice for three months until they were killed. Before that, Morris water maze, object recognition test and glucose as well as insulin tolerance test (GTT, ITT; respectively) were carried out. Protein levels and mRNA expression involved in APP processing, memory and insulin pathway were analyzed through western blotting and real-time PCR in liver and/or hippocampus. Moreover, S-Thioflavin staining was performed in order to quantify β amyloid plaques. Immunofluorescence against GFAP and IBA1 were also carried out.
EGCG treatment improved the memory decline in APP/PS1 mice fed with HFD. As expected, APP/PS1 HFD mice showed significant higher values of glucose levels in blood in both, GTT and ITT, being surprisingly reduced in the treated animals, showing no significant differences between WT and APP/PS1 HFD EGCG mice. APP/PS1 mice treated with EGCG also showed a significant decrease in the number of β amyloid plaques in cortex compared to non-treated animals. Furthermore, protein levels involved in memory processes such as PKA and p-CREB showed a significant increase only in APP/PS1 HFD mice treated with ECGC compared with APP/PS1 HFD animals. ECGC treatment also reduced astrocytes and microglial reactivity in APP/PS1 HFD.
In conclusion, our findings demonstrated that EGCG might be a potential therapeutic strategy for AD by the improvement of peripheral parameters.
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