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. 2013 Jun 3;8(6):e66069.
doi: 10.1371/journal.pone.0066069. Print 2013.

Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice

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Free PMC article

Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice

Liaoliao Li et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

Competing Interests: ZZ serves as an editor for PLOS ONE. However, this role does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.

Figures

Figure 1
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 2
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 3
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 4
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.

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