Premium
Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK‐3β in 3xTg‐AD mice
Author(s) -
Li Wei,
Wu Meijian,
Zhang Yilin,
Wei Xuemin,
Zang Jiankun,
Liu Yinghua,
Wang Yanping,
Gong ChengXin,
Wei Wei
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15105
Subject(s) - dentate gyrus , neurogenesis , intermittent fasting , gsk 3 , hippocampal formation , neurotrophic factors , hippocampus , endocrinology , brain derived neurotrophic factor , medicine , glycogen synthase , biology , signal transduction , neuroscience , microbiology and biotechnology , glycogen , receptor
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‐3β (GSK‐3β) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK‐3β 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‐3β activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK‐3β 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‐3β. 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‐3β, thus improving learning and memory.