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000156008 037__ $$aDZNE-2021-01140
000156008 041__ $$aEnglish
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000156008 1001_ $$00000-0001-7942-3273$$aMüller, Luisa$$b0
000156008 245__ $$aLong-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice.
000156008 260__ $$aBasel$$bMDPI$$c2021
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000156008 520__ $$aCaloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer's disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism-a hallmark of AD-and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.
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000156008 650_7 $$2Other$$aAPPswe/PS1delta9
000156008 650_7 $$2Other$$a[18F]FDG-PET/CT
000156008 650_7 $$2Other$$aamyloid β
000156008 650_7 $$2Other$$aautophagy
000156008 650_7 $$2Other$$acaloric restriction
000156008 650_7 $$2Other$$aiba1
000156008 650_7 $$2NLM Chemicals$$aAif1 protein, mouse
000156008 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000156008 650_7 $$2NLM Chemicals$$aCalcium-Binding Proteins
000156008 650_7 $$2NLM Chemicals$$aMicrofilament Proteins
000156008 650_7 $$2NLM Chemicals$$aRadiopharmaceuticals
000156008 650_7 $$00Z5B2CJX4D$$2NLM Chemicals$$aFluorodeoxyglucose F18
000156008 650_7 $$030KYC7MIAI$$2NLM Chemicals$$aAspartic Acid
000156008 650_7 $$0997-55-7$$2NLM Chemicals$$aN-acetylaspartate
000156008 650_7 $$0IY9XDZ35W2$$2NLM Chemicals$$aGlucose
000156008 650_7 $$0MU72812GK0$$2NLM Chemicals$$aCreatine
000156008 650_2 $$2MeSH$$aAlzheimer Disease: diet therapy
000156008 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000156008 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000156008 650_2 $$2MeSH$$aAnimal Nutritional Physiological Phenomena
000156008 650_2 $$2MeSH$$aAnimals
000156008 650_2 $$2MeSH$$aAspartic Acid: analogs & derivatives
000156008 650_2 $$2MeSH$$aAspartic Acid: metabolism
000156008 650_2 $$2MeSH$$aAutophagy: physiology
000156008 650_2 $$2MeSH$$aCalcium-Binding Proteins: metabolism
000156008 650_2 $$2MeSH$$aCaloric Restriction: methods
000156008 650_2 $$2MeSH$$aCerebral Cortex: metabolism
000156008 650_2 $$2MeSH$$aCreatine: metabolism
000156008 650_2 $$2MeSH$$aDisease Models, Animal
000156008 650_2 $$2MeSH$$aFluorodeoxyglucose F18
000156008 650_2 $$2MeSH$$aGlucose: metabolism
000156008 650_2 $$2MeSH$$aHippocampus: diagnostic imaging
000156008 650_2 $$2MeSH$$aHippocampus: metabolism
000156008 650_2 $$2MeSH$$aMagnetic Resonance Spectroscopy
000156008 650_2 $$2MeSH$$aMaze Learning
000156008 650_2 $$2MeSH$$aMice
000156008 650_2 $$2MeSH$$aMice, Inbred C3H
000156008 650_2 $$2MeSH$$aMice, Inbred C57BL
000156008 650_2 $$2MeSH$$aMice, Transgenic
000156008 650_2 $$2MeSH$$aMicrofilament Proteins: metabolism
000156008 650_2 $$2MeSH$$aNeurons: physiology
000156008 650_2 $$2MeSH$$aPlaque, Amyloid: diet therapy
000156008 650_2 $$2MeSH$$aPlaque, Amyloid: pathology
000156008 650_2 $$2MeSH$$aPositron Emission Tomography Computed Tomography
000156008 650_2 $$2MeSH$$aRadiopharmaceuticals
000156008 7001_ $$aPower Guerra, Nicole$$b1
000156008 7001_ $$aStenzel, Jan$$b2
000156008 7001_ $$aRühlmann, Claire$$b3
000156008 7001_ $$00000-0001-7826-3132$$aLindner, Tobias$$b4
000156008 7001_ $$aKrause, Bernd J$$b5
000156008 7001_ $$aVollmar, Brigitte$$b6
000156008 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b7$$udzne
000156008 7001_ $$aKuhla, Angela$$b8
000156008 770__ $$aCalorie Restriction’s Effects on Health and Disease: From Basic Research to Human Health
000156008 773__ $$0PERI:(DE-600)2518386-2$$a10.3390/nu13030985$$gVol. 13, no. 3, p. 985 -$$n3$$p985$$tNutrients$$v13$$x2072-6643$$y2021
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