TY  - JOUR
AU  - Müller, Luisa
AU  - Power Guerra, Nicole
AU  - Stenzel, Jan
AU  - Rühlmann, Claire
AU  - Lindner, Tobias
AU  - Krause, Bernd J
AU  - Vollmar, Brigitte
AU  - Teipel, Stefan
AU  - Kuhla, Angela
TI  - Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice.
JO  - Nutrients
VL  - 13
IS  - 3
SN  - 2072-6643
CY  - Basel
PB  - MDPI
M1  - DZNE-2021-01140
SP  - 985
PY  - 2021
AB  - Caloric 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.
KW  - Alzheimer Disease: diet therapy
KW  - Alzheimer Disease: pathology
KW  - Amyloid beta-Peptides: metabolism
KW  - Animal Nutritional Physiological Phenomena
KW  - Animals
KW  - Aspartic Acid: analogs & derivatives
KW  - Aspartic Acid: metabolism
KW  - Autophagy: physiology
KW  - Calcium-Binding Proteins: metabolism
KW  - Caloric Restriction: methods
KW  - Cerebral Cortex: metabolism
KW  - Creatine: metabolism
KW  - Disease Models, Animal
KW  - Fluorodeoxyglucose F18
KW  - Glucose: metabolism
KW  - Hippocampus: diagnostic imaging
KW  - Hippocampus: metabolism
KW  - Magnetic Resonance Spectroscopy
KW  - Maze Learning
KW  - Mice
KW  - Mice, Inbred C3H
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Microfilament Proteins: metabolism
KW  - Neurons: physiology
KW  - Plaque, Amyloid: diet therapy
KW  - Plaque, Amyloid: pathology
KW  - Positron Emission Tomography Computed Tomography
KW  - Radiopharmaceuticals
KW  - APPswe/PS1delta9 (Other)
KW  - [18F]FDG-PET/CT (Other)
KW  - amyloid β (Other)
KW  - autophagy (Other)
KW  - caloric restriction (Other)
KW  - iba1 (Other)
KW  - Aif1 protein, mouse (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Calcium-Binding Proteins (NLM Chemicals)
KW  - Microfilament Proteins (NLM Chemicals)
KW  - Radiopharmaceuticals (NLM Chemicals)
KW  - Fluorodeoxyglucose F18 (NLM Chemicals)
KW  - Aspartic Acid (NLM Chemicals)
KW  - N-acetylaspartate (NLM Chemicals)
KW  - Glucose (NLM Chemicals)
KW  - Creatine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33803798
C2  - pmc:PMC8003277
DO  - DOI:10.3390/nu13030985
UR  - https://pub.dzne.de/record/156008
ER  -