Department of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
Nutrition. 2022 May;97:111621. doi: 10.1016/j.nut.2022.111621. Epub 2022 Jan 30.
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.
创伤性脑损伤（TBI）后预防认知功能障碍的干预措施有限。鉴于脑损伤后成年海马神经发生有助于认知恢复，并且海马神经发生可能受到营养因素的影响，本研究旨在探讨禁食是否可以促进海马神经发生，从而改善 TBI 后的认知缺陷。
本研究使用 8-10 周龄、体重 23 克的 C57BL/6N 雄性和雌性小鼠各半。将小鼠随机分配到各组，每组 10-18 只。所有小鼠均饲养在经过批准的动物设施中，光照和黑暗周期为 12 小时。在代谢研究（食物摄入、体重、血糖、三酰甘油、总胆固醇和β-羟丁酸）中，将 54 只小鼠（雌雄比为 1:1）随机分为随意进食（AL）组（n=18）和间歇性禁食（IF）组（n=36）。在神经发生研究中，将 45 只小鼠（雌雄比为 1:1）随机分为 AL（n=18）、IF（n=9）、IF+ scramble（n=9）和 IF+神经肽 Y（NPY）_siRNA（n=9）组。在 Morris 水迷宫测试中，将 48 只小鼠（雌雄比为 1:1）随机分为 AL（n=12）、IF（n=12）、IF+ scramble（n=12）和 IF+NPY_siRNA（n=12）组。
我们表明，1 个月的 IF 方案除了改善 Morris 水迷宫测试中的认知表现外，还可增强 TBI 后海马颗粒下区神经干细胞的增殖。此外，与 AL 喂养的小鼠相比，IF 组在损伤后检测到海马 NPY 表达增加，体内局部敲低 NPY 可减弱 IF 对 TBI 的影响。
这些发现表明，IF 通过增强 NPY 表达促进 TBI 后的海马神经发生，从而减轻损伤引起的认知功能障碍。
