Intermittent fasting enhances hippocampal NPY expression to promote neurogenesis after traumatic brain injury

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2022-05, Vol.97, p.111621-111621, Article 111621
• Main Authors: Cao, Shuqiang, Li, Manrui, Sun, Yuwen, Wu, Peiyan, Yang, Wenjie, Dai, Hao, Guo, Yadong, Ye, Yi, Wang, Zheng, Xie, Xiaoqi, Chen, Xiameng, Liang, Weibo
• Format: Article
• Language: English
• Subjects: Ablation; Adult hippocampal neurogenesis; Adults; Animals; Antibodies; Body weight; Brain; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - therapy; Cell proliferation; Cholesterol; Cognition; Cognitive ability; Enzymes; Fasting; Female; Females; Food; Food intake; Gene expression; Head injuries; Hippocampus; In vivo methods and tests; Injury prevention; Intermittent fasting; Laboratory animals; Laboratory testing; Localization; Male; Males; Maze Learning; Memory; Mice; Mice, Inbred C57BL; Microscopy; Neural stem cells; Neurogenesis; Neurons - metabolism; Neuropeptide Y; Neuropeptide Y - metabolism; Neuropeptide Y - pharmacology; NPY; Proteins; RNA, Small Interfering - metabolism; RNA, Small Interfering - pharmacology; siRNA; Stem cell transplantation; Stem cells; Traumatic brain injury; Triglycerides
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2022.111621

•Intermittent fasting improved cognitive performance after traumatic brain injury.•Intermittent fasting enhanced hippocampal proliferation of neural stems cells after traumatic brain injury.•Increased hippocampal neuropeptide Y contributed to the effects of intermittent fasting. Interventions for preventing cognitive dysfunction after traumatic brain injury (TBI) are limited. Given that adult hippocampal neurogenesis after brain injury contributes to cognitive recovery, and hippocampal neurogenesis is potentially affected by nutritional factors, the aim of this study was to examine whether fasting could promote hippocampal neurogenesis and thus ameliorate the cognitive defects after TBI. The present study used 8- to 10-wk-old C57 BL/6 N mice weighing 23 g, half males and half females. The mice were randomly assigned to each group, with 10 to 18 mice per group. All mice were housed in an approved animal facility with a 12-h light/dark cycle. In the metabolic study (food intake, body weight, blood glucose, triacylglycerol, total cholesterol, and β-hydroxybutyric acid ), 54 mice (male:female = 1:1) were randomized to the ad libitum (AL) group (n = 18) and the intermittent fasting (IF) group (n = 36). In the neurogenesis study, 45 mice (male:female = 1:1) were randomized to AL (n  = 18), IF (n  = 9), IF + scramble (n  = 9), and the IF + neuropeptide Y (NPY)_siRNA (n  = 9) groups. In the Morris water maze test, 48 mice (male:female = 1:1) were randomized to AL (n  = 12), IF (n  = 12), IF + scramble (n  = 12), and the IF + NPY_siRNA (n  = 12) groups. We showed that a 1-mo-long IF regimen enhanced the proliferation of neural stem cells in the subgranular zone of the hippocampus 3 d after TBI, in addition to improving the cognitive performance in the Morris water maze test. Furthermore, an increase in the hippocampal NPY expression was detected in the IF group after the injury, compared with the mice fed AL, and local knockdown of NPY in vivo attenuated the effects of IF on TBI. These findings suggest that IF promotes hippocampal neurogenesis after TBI by a mechanism that involves enhancement of NPY expression, to alleviate cognitive dysfunction caused by injury.