Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid beta-peptide (Abeta) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD (3xTgAD mice). Groups of 3xTgAD mice were maintained on an ad libitum control diet, or CR or IF diets, beginning at 3 months of age. Half of the mice in each diet group were subjected to behavioral testing (Morris swim task and open field apparatus) at 10 months of age and the other half at 17 months of age. At 10 months 3xTgAD mice on the control diet exhibited reduced exploratory activity compared to non-transgenic mice and to 3xTgAD mice on CR and IF diets. Overall, there were no major differences in performance in the water maze among genotypes or diets in 10-month-old mice. In 17-month-old 3xTgAD mice the CR and IF groups exhibited higher levels of exploratory behavior, and performed better in both the goal latency and probe trials of the swim task, compared to 3xTgAD mice on the control diet. 3xTgAD mice in the CR group showed lower levels of Abeta1-40, Abeta1-42 and phospho-tau in the hippocampus compared to the control diet group, whereas Abeta and phospho-tau levels were not decreased in 3xTgAD mice in the IF group. IF may therefore protect neurons against adverse effects of Abeta and tau pathologies on synaptic function. We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies.
Halagappa
Veerendra Kumar Madala
VK
Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA.
Guo
Zhihong
Z
Pearson
Michelle
M
Matsuoka
Yasuji
Y
Cutler
Roy G
RG
Laferla
Frank M
FM
Mattson
Mark P
MP
D000375:Aging / Q000523:psychology*; D000544:Alzheimer Disease / Q000178:diet therapy* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction / Q000523:psychology*; D005215:Fasting / Q000523:psychology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins