期刊
JOURNAL OF NEUROCHEMISTRY
卷 155, 期 6, 页码 697-713出版社
WILEY
DOI: 10.1111/jnc.15105
关键词
GSK-3 beta; insulin pathway; Intermittent fasting; neuronal differentiation
资金
- National Natural Science Foundation of China [81100944, 2018A030313565, 201904010040]
- Natural Science Foundation of Guangdong Province
- Scientific and Technological Planning Program of Guangzhou
Moderate dietary restriction can ameliorate age-related chronic diseases such as Alzheimer's disease (AD) by increasing the expression of neurotrophic factors and promoting neurogenesis in the brain. Glycogen synthase kinase-3 beta (GSK-3 beta) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK-3 beta is involved in dietary restriction-induced neurogenesis and cognitive improvement remain unclear. Six-month-old male 3xTg-AD and wild-type mice were fed on alternate days (intermittent fasting, IF) or ad libitum (AL) for 3 months. GSK-3 beta activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK-3 beta into the dentate gyrus region of the hippocampus. Intermittent fasting promoted neuronal differentiation and maturation in the dentate gyrus and ameliorated recognized dysfunction in 3xTg-AD mice. These effects were reversed by siRNA targeting GSK-3 beta. After intermittent fasting, the insulin and protein kinase A signaling pathways were inhibited, while the adenosine monophosphate-activated protein kinase and brain-derived neurotrophic factor pathways were activated. These findings suggest that intermittent fasting can promote neuronal differentiation and maturation in the hippocampus by activating GSK-3 beta, thus improving learning and memory.
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