TY - JOUR
T1 - Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis and expression of longevity gene Klotho
AU - Pereira Dias, Gisele
AU - Murphy, Tytus
AU - Stangl, Doris
AU - Ahmet, Selda
AU - Morisse, Benjamin
AU - Nix, Alina
AU - Aimone, Lindsey J.
AU - Aimone, James B.
AU - Kuro-O, Makoto
AU - Gage, Fred H.
AU - Thuret, Sandrine
N1 - Funding Information:
Acknowledgements The authors are grateful for the grants provided by the Research Council UK, the Medical Research Council (MR/ K500811/1 and MR/N030087/1), the Psychiatry Research Trust, the Brazilian Council for Scientific and Technological Development (CNPq – Science without Borders Program; 244420/2012-2), the Rio de Janeiro Research Foundation (FAPERJ), the Japan Agency for Medical Research and Development, Grant number JP19gm0610012, the JPB Foundation, the Ray & Dagmar Dolby Family Fund, and the AHA-Allen initiative in brain health and cognitive impairment or funding collectively the research carried out in this article.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/5/25
Y1 - 2021/5/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85106329006&partnerID=8YFLogxK
U2 - 10.1038/s41380-021-01102-4
DO - 10.1038/s41380-021-01102-4
M3 - Article
SN - 1359-4184
VL - 26
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 11
ER -