Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK‐3β in 3xTg‐AD mice

Li, Wei; Wu, Meijian; Zhang, Yilin; Wei, Xuemin; Zang, Jiankun; Liu, Yinghua; Wang, Yanping; Chen, Gong; Wei, Wei

doi:10.1111/jnc.15105

Cited by 22 publications

(28 citation statements)

References 96 publications

(128 reference statements)

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“…Upon close examination of the available literature on IF in rodents, we wonder whether publication bias might be playing a role in skewing it towards reporting positive results. We noticed high diversity in its effects on adult neurogenesis, with an overwhelming majority of reports showing variable positive impact (Apple et al, 2019;Baik et al, 2020;Brandhorst et al, 2015;Cao et al, 2022;Dias et al, 2021;Kaptan et al, 2015;Kim et al, 2015;Kitamura et al, 2006;Kumar et al, 2009;Lee et al, 2000;Lee et al, 2002b;Lee et al, 2002a;Li et al, 2020;Park et al, 2013;Wu et al, 2008) and very few showing no effect or a mild impairment (Bondolfi et al, 2004;Staples et al, 2017). In some reviews, even studies reporting no effect are cited as evidence for improved neurogenesis upon IF.…”

Section: Discussionmentioning

confidence: 99%

Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Gabarró-Solanas

Davaatseren

Kepcija

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Gabarró-Solanas

Davaatseren

Kepcija

et al. 2022

Preprint

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“…Caloric restriction is a particularly important confounding factor to consider when comparing TAM chow-fed to vehicle chow-fed animals. Although Bondolfi and colleagues found no effect of caloric restriction on hippocampal neurogenesis in male mice aged 3–11 months ( Bondolfi et al, 2004 ), others have found that dietary restriction and intermittent fasting enhance neuronal differentiation in the adult hippocampus ( Hornsby et al, 2016 ; Li et al, 2020 ). Both the caloric restriction during TAM feeding and the return to normal feeding after the end of TAM chow may therefore be affecting neurogenesis in TAM-fed mice.…”

Section: Discussionmentioning

confidence: 99%

Oral and injected tamoxifen alter adult hippocampal neurogenesis in female and male mice

Smith

Saulsbery

Sarchet

et al. 2022

eNeuro

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“…Caloric restriction is a particularly important confounding factor to consider when comparing TAM chow-fed to vehicle chow-fed animals. Though Bondolfi et al found no effect of caloric restriction on hippocampal neurogenesis in male mice aged 3-11 months (Bondolfi et al, 2004), others have found that dietary restriction and intermittent fasting enhance neuronal differentiation in the adult hippocampus (Hornsby et al, 2016; Li et al, 2020). Both the caloric restriction during TAM feeding and the return to normal feeding after the end of TAM chow may therefore be affecting neurogenesis in TAM-fed mice.…”

Section: Discussionmentioning

confidence: 99%

Oral and injected tamoxifen alter adult hippocampal neurogenesis in female and male mice

Smith

Saulsbery

Sarchet

et al. 2021

Preprint

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Inducible Cre recombinase facilitates temporal control of genetic recombination in numerous transgenic model systems, a feature which has made it a popular tool for studies of adult neurogenesis. One of the most common forms of inducible Cre, CreERT2, requires activation by the synthetic estrogen tamoxifen (TAM) to initiate recombination of LoxP-flanked sequences. To date, most studies deliver TAM via intraperitoneal injection. But the introduction of TAM-infused commercial chows has recently expanded the possible modes of TAM delivery. Despite the widespread use of TAM-inducible genetic models in adult neurogenesis research, the comparative efficiency and off-target effects of TAM administration protocols is surprisingly infrequently studied. Here we compare a standard, 5 day TAM injection regimen with voluntary consumption of TAM-infused chow. First, we used adult NestinCreERT2;Rosa-LoxP-STOP-LoxP-EYFP reporter mice to show that 2 weeks of TAM chow and 5 days of injections led to LoxP recombination in a similar phenotypic population of neural stem and progenitor cells in the adult dentate gyrus. However, TAM chow resulted in substantially less overall recombination than injections. TAM administration also altered adult neurogenesis, but in different ways depending on administration route: TAM injection disrupted neural progenitor cell proliferation 3 weeks after TAM, whereas TAM chow increased neuronal differentiation of cells generated during the diet period. These findings provide guidance for selection of TAM administration route and appropriate controls in adult neurogenesis studies using TAM-inducible Cre mice. They also highlight the need for better understanding of off-target effects of TAM in other neurological processes and organ systems.

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Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK‐3β in 3xTg‐AD mice

Cited by 22 publications

References 96 publications

Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Oral and injected tamoxifen alter adult hippocampal neurogenesis in female and male mice

Oral and injected tamoxifen alter adult hippocampal neurogenesis in female and male mice

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