Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Abstract

Intermittent fasting (IF) is a promising non-pharmacological strategy to counteract ageing which has been shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is still unclear which steps of the adult neurogenesis process are regulated by IF. The number of adult neural stem cells (NSCs) decreases with age in an activation-dependent manner. To counteract the loss of the stem cell pool, adult NSCs are mostly found in an inactive, quiescent state which ensures their long-term maintenance. We aimed to determine if and how IF impacts the activity and maintenance of adult NSCs in the hippocampus. We chose an every-other-day fasting protocol with food re-administration at night, which we found effectively induces fasting features and preserves the circadian activity pattern of mice. To determine the effects of IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We found that IF does not affect NSC activation or maintenance. Contrary to previous reports, we also found that IF does not increase hippocampal neurogenesis. We obtained the same results regardless of strain, sex, diet length, tamoxifen administration or new-born neuron identification method. Our data suggest that NSCs maintain homeostasis upon IF and that this intervention is not a reliable strategy to increase adult neurogenesis.

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice

“…Collectively, our findings and those of Gabarró-Solanas et al, (2022) do not align with other studies on DR and neurogenesis. However, variations in the age and sex of animals used in each of these studies limit the value of direct comparisons.…”

“…Interestingly, a recent pre-print from Gabarró-Solanas et al, (2022) questions the suitability of ADF as a pro-neurogenic intervention, with neither 1-month or 3-months of ADF stimulating AHN. Utilising a tamoxifen inducible transgenic model (Glast-CreER T2 ;RYFP mice) to trace NSC lineage, ADF did not enhance NSC proliferation (as determined by Ki67 expression and Edu incorporation), nor the abundance of immature neurones (DCX + cells).…”

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice

“…Interestingly, in this issue of EMBO Reports, Gabarro‐Solanas et al (2023) questions the suitability of ADF as a pro‐neurogenic intervention, with neither 1‐month nor 3‐months of ADF stimulating AHN. Utilising a tamoxifen inducible transgenic model to trace NSC lineage, ADF did not enhance NSC proliferation, nor the abundance of immature neurones.…”