Intermittent fasting ameliorates neuronal ferroptosis and cognitive impairment in mice after traumatic brain injury

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2023-05, Vol.109, p.111992-111992, Article 111992
• Main Authors: Yang, Qiuyun, Li, Manrui, Liu, Jinyuan, Zhang, Lingxuan, Yuan, Ruixuan, Xu, Yang, Zheng, Jingwen, Cao, Shuqiang, Dai, Hao, Liao, Miao, Lv, Meili, Chen, Xiaogang, Guo, Yadong, Xie, Xiaoqi, Zhang, Lin, Chen, Xiameng, Liang, Weibo
• Format: Article
• Language: English
• Subjects: Animal cognition; Animal memory; Animal models; Animals; Apoptosis; Brain; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - metabolism; Cell death; Cognition; Cognitive ability; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; Cortex; CYBB protein; Fasting; Ferroptosis; Head injuries; Impairment; Injury prevention; Intermittent Fasting; Laboratory animals; Lipid peroxidation; Lipids; Mice; Mitochondria; Neurons - metabolism; Pathogenesis; Peroxidation; Pigments; Staining; Traumatic brain injury
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2023.111992

•One month of intermittent fasting changes the expression of ferroptosis genes after traumatic brain injury.•Intermittent fasting alleviates the characteristic cellular damage induced by ferroptosis after traumatic brain injury.•Intermittent fasting improves cognitive function of mice subjected to traumatic brain injury. Ferroptosis, a newly characterized form of programmed cell death that results from lipid peroxidation and mitochondrial dysfunction, has been demonstrated to be involved in the pathogenesis of traumatic brain injury (TBI). Scientific evidence has shown that intermittent fasting (IF) reduces both the lipid peroxidation and the mitochondrial dysfunction, raising the question of whether IF affects the ferroptosis induced by TBI. Here, based on an established TBI animal model, we examine the effects of IF on the activation of ferroptosis pathway as well as related outcomes. We uncovered that a 1-mo IF elevated the protective Gpx4 and Hspb1 expression, and partly abolished the increase of Nfe2l2, Slc7a11, Alox8, Steap3, and Nox2 in the cortex, which were induced by TBI. Furthermore, the characteristic cellular damage induced by ferroptosis was alleviated by IF, as revealed by Perls’ Prussian blue staining, Nissl staining, and transmission electron microscope examination. Consistently, we examined the outcomes of mice subjected to TBI and found an improved cognitive function of the IF mice. In sum, our study demonstrated, to our knowledge for the first time, that a 1-mo IF regimen partly ameliorates ferroptosis in the cortex of mice subjected to TBI, which potentially contributes to a lessening of cognitive impairment.