Journal
FRONTIERS IN AGING NEUROSCIENCE
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2022.998292
Keywords
chronic sleep deprivation; Alzheimer's disease; ketogenic diet (KD); ferroptosis; SIRT1; Nrf2
Categories
Funding
- Natural Science Foundation of Shandong Province [ZR2021QH022]
- Open Project of Liaocheng University Animal Husbandry Discipline [319312101-29]
- Open Project of Shandong Collaborative Innovation Center for Antibody Drugs [CIC-AD1842]
Ask authors/readers for more resources
This study firstly suggested that ketogenic diet (KD) can prevent sleep deprivation (SD)-induced Alzheimer's disease (AD) by activating the Sirt1/Nrf2 signaling pathway.
Sleep deprivation (SD) is one of the main risk factors for Alzheimer's disease (AD), but the underlying mechanism is still unclear. Ketogenic diet (KD) has been shown widely neuroprotective effects but less known about its effect on SD-induced AD. In the present study, a continuous 21 days SD mouse model with or without KD was established. The changes of cognitive function, pathological hallmarks of AD, ferroptosis, and intracellular signal pathways in mice were detected by Morris water maze, ThS staining, diaminobenzidine (DAB)-enhanced Perls' stain, antioxidant assay, immuno-histochemistry, and western blot. The results showed that KD can prevent the cognitive deficiency, amyloid deposition and hyperphosphorylated tau induced by chronic SD. Analysis of ferroptosis revealed that KD can inhibit iron dyshomeostasis by down-regulating the expression of TfR1 and DMT1 and up-regulating the expression of FTH1, FPN1. Meanwhile, KD alleviated oxidative stress with elevated xCT/GPX4 axis, FSP1 and reduced MDA. In addition, KD could promote neuronal repair by enhancing BDNF and DCX. Further studies demonstrated that KD activated Sirt1/Nrf2 signaling pathway in the hippocampus in SD-exposed mice. Our finding firstly suggested that KD could prevent chronic SD-induced AD by inhibiting ferroptosis and improving the neuronal repair ability via Sirt1/Nrf2 signaling pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available