| First Author | Li W | Year | 2020 |
| Journal | J Neurochem | Volume | 155 |
| Issue | 6 | Pages | 697-713 |
| PubMed ID | 32578216 | Mgi Jnum | J:304693 |
| Mgi Id | MGI:6514543 | Doi | 10.1111/jnc.15105 |
| Citation | Li W, et al. (2020) Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK-3beta in 3xTg-AD mice. J Neurochem 155(6):697-713 |
| abstractText | 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-3beta (GSK-3beta) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK-3beta 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-3beta activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK-3beta 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-3beta. 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-3beta, thus improving learning and memory. |
