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Epigallocatechin-3-Gallate (EGCG) Improves Cognitive Deficits Aggravated by an Obesogenic Diet Through Modulation of Unfolded Protein Response in APPswe/PS1dE9 Mice

dc.contributor.authorEttcheto M.
dc.contributor.authorCano A.
dc.contributor.authorManzine P.R.
dc.contributor.authorBusquets O.
dc.contributor.authorVerdaguer E.
dc.contributor.authorCastro-Torres R.D.
dc.contributor.authorGarcía M.L.
dc.contributor.authorBeas-Zarate C.
dc.contributor.authorOlloquequi J.
dc.contributor.authorAuladell C.
dc.contributor.authorFolch J.
dc.contributor.authorCamins A.
dc.date.accessioned2020-09-02T22:17:21Z
dc.date.available2020-09-02T22:17:21Z
dc.date.issued2020
dc.identifier10.1007/s12035-019-01849-6
dc.identifier.citation57, 4, 1814-1827
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4410
dc.descriptionEpigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been previously investigated for its neuroprotective effects in vitro and in vivo. In the present study, we aimed to evaluate its possible beneficial effects in a well-established preclinical mixed model of familial Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) based on the use of transgenic APPswe/PS1dE9 (APP/PS1) mice fed with a high fat diet (HFD). C57BL/6 wild-type (WT) and APP/PS1 mice were used in this study. APP/PS1 mice were fed with a palmitic acid–enriched HFD (APP/PS1 HFD) containing 45% of fat mainly from hydrogenated coconut oil. Intraperitoneal glucose tolerance tests (IP-GTT) and insulin tolerance tests (IP-ITT) were performed. Western blot analyses were performed to analyse protein expression, and water maze and novel object recognition test were done to evaluate the cognitive process. EGCG treatment improves peripheral parameters such as insulin sensitivity or liver insulin pathway signalling, as well as central memory deficits. It also markedly increased synaptic markers and cAMP response element binding (CREB) phosphorylation rates, as a consequence of a decrease in the unfolded protein response (UPR) activation through the reduction in the activation factor 4 (ATF4) levels and posterior downregulation of protein tyrosine phosphatase 1B (PTP1B). Moreover, EGCG significantly decreased brain amyloid β (Aβ) production and plaque burden by increasing the levels of α-secretase (ADAM10). Also, it led to a reduction in neuroinflammation, as suggested by the decrease in astrocyte reactivity and toll-like receptor 4 (TLR4) levels. Collectively, evidence suggests that chronic EGCG prevents distinct neuropathological AD-related hallmarks. This study also provides novel insights into the metabolic and neurobiological mechanisms of EGCG against cognitive loss through its effects on UPR function, suggesting that this compound may be a promising disease-modifying treatment for neurodegenerative diseases. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
dc.language.isoen
dc.publisherSpringer
dc.subjectAPPswe/PS1dE9 mice
dc.subjectCognitive deficits
dc.subjectEpigallocatechin-3-gallate
dc.subjectHippocampus
dc.subjectObesity
dc.subjectUnfolded protein response
dc.subjectactivating transcription factor 4
dc.subjectADAM10 endopeptidase
dc.subjectamyloid beta protein
dc.subjectcyclic AMP responsive element binding protein
dc.subjectepigallocatechin gallate
dc.subjectpalmitic acid
dc.subjectprotein tyrosine phosphatase 1B
dc.subjecttoll like receptor 4
dc.subjectAlzheimer disease
dc.subjectamyloid plaque
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectastrocyte
dc.subjectcognitive defect
dc.subjectcontrolled study
dc.subjectdown regulation
dc.subjectdrug distribution
dc.subjectglucose tolerance test
dc.subjectinsulin sensitivity
dc.subjectinsulin signaling
dc.subjectinsulin tolerance test
dc.subjectlipid diet
dc.subjectmale
dc.subjectmemory disorder
dc.subjectMorris water maze test
dc.subjectmouse
dc.subjectnervous system inflammation
dc.subjectneuroprotection
dc.subjectnon insulin dependent diabetes mellitus
dc.subjectnonhuman
dc.subjectnovel object recognition test
dc.subjectobesogenic diet
dc.subjectprotein expression
dc.subjectprotein phosphorylation
dc.subjectsynapse
dc.subjectunfolded protein response
dc.subjectWestern blotting
dc.titleEpigallocatechin-3-Gallate (EGCG) Improves Cognitive Deficits Aggravated by an Obesogenic Diet Through Modulation of Unfolded Protein Response in APPswe/PS1dE9 Mice
dc.typeArticle


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