Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice
| Autor: | Tobias Lindner, Jan Stenzel, Angela Kuhla, Claire Rühlmann, Bernd J. Krause, Stefan J. Teipel, Brigitte Vollmar, Nicole Power Guerra, Luisa Müller |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Magnetic Resonance Spectroscopy Glucose uptake Morris water navigation task metabolism [Hippocampus] Plaque Amyloid Hippocampal formation Microgliosis Hippocampus pathology [Alzheimer Disease] Mice iba1 N-acetylaspartate 0302 clinical medicine Positron Emission Tomography Computed Tomography Hippocampus (mythology) [18F]FDG-PET/CT diagnostic imaging [Hippocampus] Cerebral Cortex Neurons Mice Inbred C3H Nutrition and Dietetics Chemistry Microfilament Proteins methods [Caloric Restriction] APPswe/PS1delta9 physiology [Neurons] metabolism [Glucose] diet therapy [Plaque Amyloid] amyloid β Animal Nutritional Physiological Phenomena caloric restriction diet therapy [Alzheimer Disease] lcsh:Nutrition. Foods and food supply medicine.medical_specialty autophagy physiology [Autophagy] metabolism [Amyloid beta-Peptides] lcsh:TX341-641 Mice Transgenic Neuropathology Neuroprotection Article 03 medical and health sciences Alzheimer Disease Fluorodeoxyglucose F18 Internal medicine medicine Animals ddc:610 pathology [Plaque Amyloid] Maze Learning Caloric Restriction analogs & derivatives [Aspartic Acid] metabolism [Creatine] Aspartic Acid Amyloid beta-Peptides Aif1 protein mouse metabolism [Cerebral Cortex] Autophagy Calcium-Binding Proteins metabolism [Microfilament Proteins] metabolism [Calcium-Binding Proteins] Creatine metabolism [Aspartic Acid] Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Glucose Radiopharmaceuticals 030217 neurology & neurosurgery Food Science |
| Zdroj: | Nutrients Nutrients 13(3), 985-(2021). doi:10.3390/nu13030985 Volume 13 Issue 3 Nutrients, Vol 13, Iss 985, p 985 (2021) |
| ISSN: | 2072-6643 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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