1. Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho
- Author
-
Sandrine Thuret, Selda Ahmet, Tytus Murphy, Lindsey J Aimone, Alina Nix, James B. Aimone, Gisele Pereira Dias, Doris Stangl, Benjamin Morisse, Makoto Kuro-o, and Fred H. Gage
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Memory, Long-Term ,Neurogenesis ,Calorie restriction ,Hippocampus ,Stem cells ,Hippocampal formation ,Biology ,Article ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Neuroblast ,Internal medicine ,Intermittent fasting ,medicine ,Animals ,Molecular Biology ,Klotho ,Memory Consolidation ,Fasting ,Mice, Inbred C57BL ,Psychiatry and Mental health ,030104 developmental biology ,Endocrinology ,Knockout mouse ,Female ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
- Published
- 2021
- Full Text
- View/download PDF