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Cited by 147Dietary Effects on HealthGenetics, Aging, and Longevity in Model OrganismsNeurological Disease Mechanisms and Treatments

The DOI matches its Crossref record; 21 of the 23 references it cites were found in a registry or an index.

Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice

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Li, Liaoliao, Wang, Zhi, Zuo, Zhiyi·2013·PLoS ONE
DOI 10.1371/journal.pone.0066069PMC PMC3670843
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Abstract

Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

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Crossref · 10.1371/journal.pone.0066069

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Figure 1 The effects of various feeding protocols on body weights and blood chemicals. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. Their growth curves are presented in panel A. Their blood was drawn at the end of the 11-month feeding to measure lipid profiles (panels B and C), glucose, albumin and creatinine (panel D). Results are means ± S.E.M (n = 12 – 15). * P<0.05 compared with mice on regular chow ad libitum. HDL: high density lipoprotein; LDL: low density lipoprotein.
Figure 1 The effects of various feeding protocols on body weights and blood chemicals. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. Their growth curves are presented in panel A. Their blood was drawn at the end of the 11-month feeding to measure lipid profiles (panels B and C), glucose, albumin and creatinine (panel D). Results are means ± S.E.M (n = 12 – 15). * P<0.05 compared with mice on regular chow ad libitum. HDL: high density lipoprotein; LDL: low density lipoprotein.CC BY · PubMed Central
Figure 2 The effects of various feeding protocols on leaning and memory. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. They were then subjected to Barnes maze, fear conditioning and rotarod tests. The results in the training sessions and memory phase of the Barnes maze are presented in panels A and B. The fear conditioning and rotarod results are shown in panels C and D, respectively. Results are means ± S.E.M (n = 15 – 35). * P<0.05 compared with mice on regular chow ad libitum.
Figure 2 The effects of various feeding protocols on leaning and memory. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. They were then subjected to Barnes maze, fear conditioning and rotarod tests. The results in the training sessions and memory phase of the Barnes maze are presented in panels A and B. The fear conditioning and rotarod results are shown in panels C and D, respectively. Results are means ± S.E.M (n = 15 – 35). * P<0.05 compared with mice on regular chow ad libitum.CC BY · PubMed Central
Figure 3 The effects of various feeding protocols on CA1 pyramidal cell layer thickness, neuron-specific proteins and brain derived neurotrophic factor (BDNF) in the brain. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. Their brains were then harvested to measure CA1 pyramidal cell layer thickness (panel A) and expression of NeuN, drebrin and synaptophysin in the cerebral cortex (panel B) and hippocampus (panel C) as well as the BDNF levels in the cerebral cortex and hippocampus (panel D). The protein abundance results in each mouse were normalized by the mean value of the corresponding protein in the regular diet-fed mice. Results are means ± S.E.M (n = 7 – 12). * P<0.05 compared with mice on regular diet ad libitum. GAPDH: glyceraldehydes 3-phosphate dehydrogenase; Hippo: hippocampus; SP: synaptophysin; RD: regular diet; IF: intermittent fasting; HFD: high fat diet.
Figure 3 The effects of various feeding protocols on CA1 pyramidal cell layer thickness, neuron-specific proteins and brain derived neurotrophic factor (BDNF) in the brain. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. Their brains were then harvested to measure CA1 pyramidal cell layer thickness (panel A) and expression of NeuN, drebrin and synaptophysin in the cerebral cortex (panel B) and hippocampus (panel C) as well as the BDNF levels in the cerebral cortex and hippocampus (panel D). The protein abundance results in each mouse were normalized by the mean value of the corresponding protein in the regular diet-fed mice. Results are means ± S.E.M (n = 7 – 12). * P<0.05 compared with mice on regular diet ad libitum. GAPDH: glyceraldehydes 3-phosphate dehydrogenase; Hippo: hippocampus; SP: synaptophysin; RD: regular diet; IF: intermittent fasting; HFD: high fat diet.CC BY · PubMed Central
Figure 4 The effects of various feeding protocols on oxidative stress status in the brain. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. Their brains were then harvested to measure glutathione (GSH), glutathione disulfide (GSSG), 4-hydroxy-2-nonenal (HNE) and nitrotyrosine containing proteins. The levels of GSH and GSSG and ratio of GSH/GSSG in the cerebral cortex and hippocampus are presented in panels A and B, respectively. The levels of HNE and nitrotyrosine containing proteins in the cerebral cortex and hippocampus are shown in the panels C and D. Results are means ± S.E.M (n = 8). * P<0.05 compared with mice on regular chow ad libitum.
Figure 4 The effects of various feeding protocols on oxidative stress status in the brain. Seven-week old male mice had free access to regular chow or high fat diet or were allowed to have free access to regular chow every other day (intermittent fasting) for 11 months. Their brains were then harvested to measure glutathione (GSH), glutathione disulfide (GSSG), 4-hydroxy-2-nonenal (HNE) and nitrotyrosine containing proteins. The levels of GSH and GSSG and ratio of GSH/GSSG in the cerebral cortex and hippocampus are presented in panels A and B, respectively. The levels of HNE and nitrotyrosine containing proteins in the cerebral cortex and hippocampus are shown in the panels C and D. Results are means ± S.E.M (n = 8). * P<0.05 compared with mice on regular chow ad libitum.CC BY · PubMed Central

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Metadata

Authors
Li, L., Wang, Z., & Zuo, Z.
Affiliations
  • University of Virginia (US)
  • Sun Yat-sen University (CN)
Corresponding author
Zuo, Zhiyi
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-06-03
Volume
8
Issue
6
Pages
e66069
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0066069
PMC
PMC3670843
OpenAlex
W1974661288
Cited by
147
References
23
Citations by year
2026: 7 · 2025: 15 · 2024: 13 · 2023: 13 · 2022: 19 · 2021: 14 · 2020: 19 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 6
FWCI
5.34
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Heart Association (10GRNT3900019)
  • International Anesthesia Research Society (R01 GM065211)
  • National Institutes of Health (GM098308)
  • National Institute of General Medical Sciences (R01GM065211, R01GM098308)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
intermittent fasting, alternate-day fasting, cognitive function, learning and memory, brain aging, high-fat diet, obesity, drebrin, oxidative stress, hyperlipidemia, exercise tolerance, Barnes maze, fear conditioning, middle-aged mice
MeSH terms
Aging, Animals, Cerebral Cortex, Cognition, Dietary Fats, Fasting, Male, Memory, Mice, Obese, Neuropeptides, Obesity, Exercise Tolerance, Oxidative Stress, Maze Learning, Mice, CA1 Region, Hippocampal, Diet, High-Fat

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