Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho.

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.

SUBMITTER: Dias GP

PROVIDER: S-EPMC8760057 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Memory consolidation during sleep and adult hippocampal neurogenesis.

Project description:In anticipation of the massive burden of neurodegenerative disease within super-aged societies, great efforts have been made to utilize neural stem and progenitor cells for regenerative medicine. The capacity of intrinsic neural stem and progenitor cells to regenerate damaged brain tissue remains unclear, due in part to the lack of knowledge about how these newly born neurons integrate into functional circuitry. As sizable integration of adult-born neurons naturally occurs in the dentate gyrus region of the hippocampus, clarifying the mechanisms of this process could provide insights for applying neural stem and progenitor cells in clinical settings. There is convincing evidence of functional correlations between adult-born neurons and memory consolidation and sleep; therefore, we describe some new advances that were left untouched in our recent review.

| S-EPMC6263001 | biostudies-literature

Disruption of NREM sleep and sleep-related spatial memory consolidation in mice lacking adult hippocampal neurogenesis.

Project description:Cellular plasticity at the structural level and sleep at the behavioural level are both essential for memory formation. The link between the two is not well understood. A functional connection between adult neurogenesis and hippocampus-dependent memory consolidation during NREM sleep has been hypothesized but not experimentally shown. Here, we present evidence that during a three-day learning session in the Morris water maze task a genetic knockout model of adult neurogenesis (Cyclin D2-/-) showed changes in sleep macro- and microstructure. Sleep EEG analyses revealed a lower total sleep time and NREM fraction in Cyclin D2-/- mice as well as an impairment of sleep specific neuronal oscillations that are associated with memory consolidation. Better performance in the memory task was associated with specific sleep parameters in wild-type, but not in Cyclin D2-/- mice. In wild-type animals the number of proliferating cells correlated with the amount of NREM sleep. The lack of adult neurogenesis led to changes in sleep architecture and oscillations that represent the dialog between hippocampus and neocortex during sleep. We suggest that adult neurogenesis-as a key event of hippocampal plasticity-might play an important role for sleep-dependent memory consolidation and modulates learning-induced changes of sleep macro- and microstructure.

| S-EPMC7536189 | biostudies-literature

Deregulated expression of a longevity gene, Klotho, in the C9orf72 deletion mice with impaired synaptic plasticity and adult hippocampal neurogenesis.

Project description:Hexanucleotide repeat expansion of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Synergies between loss of C9ORF72 functions and gain of toxicities from the repeat expansions contribute to C9ORF72-mediated pathogenesis. However, how loss of C9orf72 impacts neuronal and synaptic functions remains undetermined. Here, we showed that long-term potentiation at the dentate granule cells and long-term depression at the Schaffer collateral/commissural synapses at the area CA1 were reduced in the hippocampus of C9orf72 knockout mice. Using unbiased transcriptomic analysis, we identified that Klotho, a longevity gene, was selectively dysregulated in an age-dependent manner. Specifically, Klotho protein expression in the hippocampus of C9orf72 knockout mice was incorrectly enriched in the dendritic regions of CA1 with concomitant reduction in granule cell layer of dentate gyrus at 3-month of age followed by an accelerating decline during aging. Furthermore, adult hippocampal neurogenesis was reduced in C9orf72 knockout mice. Taken together, our data suggest that C9ORF72 is required for synaptic plasticity and adult neurogenesis in the hippocampus and Klotho deregulations may be part of C9ORF72-mediated toxicity.

| S-EPMC7473815 | biostudies-literature

Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Project description:Intermittent fasting (IF) is a promising strategy to counteract ageing shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is 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 this loss, adult NSCs are found in a quiescent state which ensures their long-term maintenance. We aimed to determine if and how IF affects adult NSCs in the hippocampus. To identify the effects of every-other-day IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We show here that IF does not affect NSC activation or maintenance. Contrary to previous reports, IF does not increase neurogenesis. The same results are obtained 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.

| S-SCDT-10_15252-EMBR_202357268 | biostudies-other

Spatial relational memory requires hippocampal adult neurogenesis.

Project description:The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

| S-EPMC2396793 | biostudies-literature

Updating stored memory requires adult hippocampal neurogenesis.

Project description:Adult hippocampal neurogenesis appears to influence hippocampal functions, such as memory formation for example. While adult hippocampal neurogenesis is known to be involved in hippocampal-dependent learning and consolidation processes, the role of such immature neurons in memory reconsolidation, a process involved in the modification of stored memories, remains unclear. Here, using a novel fast X-ray ablation protocol to deplete neurogenic cells, we have found that adult hippocampal neurogenesis is required to update object recognition stored memory more than to reinforce it. Indeed, we show that immature neurons were selectively recruited to hippocampal circuits during the updating of stored information. Thus, our data demonstrate a new role for neurogenesis in cognitive processes, adult hippocampal neurogenesis being required for the updating of stored OR memories. These findings suggest that manipulating adult neurogenesis may have a therapeutic application in conditions associated with traumatic stored memory, for example.

| S-EPMC4566137 | biostudies-literature

Adult neural stem cells and neurogenesis are resilient to intermittent fasting.

Project description:Intermittent fasting (IF) is a promising strategy to counteract ageing shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is 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 and, to counteract this loss, adult NSCs are found in a quiescent state which ensures their long-term maintenance. We aimed to determine if and how IF affects adult NSCs in the hippocampus. To identify the effects of every-other-day IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We show here that IF does not affect NSC activation or maintenance and, that contrary to previous reports, IF does not increase neurogenesis. The same results are obtained 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.

| S-EPMC10702802 | biostudies-literature

Modulation of Aversive Memory by Adult Hippocampal Neurogenesis.

Project description:Adult hippocampal neurogenesis (AHN) occurs in humans and every other mammalian species examined. Evidence that AHN is stimulated by a variety of treatments and behaviors with anxiolytic properties has sparked interest in harnessing AHN to treat anxiety disorders. However, relatively little is known about the mechanisms through which AHN modulates fear and anxiety. In this review, we consider evidence that AHN modulates fear and anxiety by altering the processing of and memory for traumatic experiences. Based on studies of the role of AHN in Pavlovian fear conditioning, we conclude that AHN modulates the consequences of aversive experience by influencing 1) the efficiency of hippocampus-dependent memory acquisition; 2) generalization of hippocampal fear memories; 3) long-term retention of hippocampal aversive memories; and 4) the nonassociative effects of acute aversive experience. The preclinical literature suggests that stimulation of AHN is likely to have therapeutically relevant consequences, including reduced generalization and long-term retention of aversive memories. However, the literature also identifies four caveats that must be addressed if AHN-based therapies are to achieve therapeutic benefits without significant side effects.

| S-EPMC5509626 | biostudies-literature

Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner.

Project description:The beneficial effects of calorie restriction (CR) have been described at both organismal and cellular levels in multiple organs. However, our understanding of the causal mediators of such hormesis is poorly understood, particularly in the context of higher brain function. Here, we show that the receptor for the orexigenic hormone acyl-ghrelin, the growth hormone secretagogue receptor (Ghsr), is enriched in the neurogenic niche of the hippocampal dentate gyrus (DG). Acute elevation of acyl-ghrelin levels by injection or by overnight CR, increased DG levels of the neurogenic transcription factor, Egr-1. Two weeks of CR increased the subsequent number of mature newborn neurons in the DG of adult wild-type but not Ghsr(-/-) mice. CR wild-type mice also showed improved remote contextual fear memory. Our findings suggest that Ghsr mediates the beneficial effects of CR on enhancing adult hippocampal neurogenesis and memory.

| S-EPMC4686051 | biostudies-literature

GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal BDNF levels.

Project description:Memory consolidation is the process by which acquired information is converted to something concrete to be retrieved later. Here we examined a potential role for brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory consolidation induced by the GABA(A) receptor antagonist, bicuculline methiodide. With the administration of an acquisition trial in naïve mice using a passive avoidance task, mature BDNF (mBDNF) levels were temporally changed in the hippocampal CA1 region, and the lowest levels were observed 9?h after the acquisition trial. In the passive avoidance task, bicuculline methiodide administration within 1?h of training but not after 3?h significantly increased latency time in the retention trial 24?h after the acquisition trial. Concomitantly, 1?h post-training administration of bicuculline methiodide, which enhanced memory consolidation, significantly increased mBDNF levels 9?h after training compared to those of the vehicle-treated control group. In addition, exogenous human recombinant BDNF (hrBDNF) administration 9?h after training into the hippocampal CA1 region facilitated memory consolidation confirming that the increase in mBDNF at around 9?h after training plays a key role in the enhancement of memory consolidation. Moreover, the increases in latency time and immediate early gene expressions by bicuculline methiodide or hrBDNF were significantly blocked by anisomycin, a protein synthesis inhibitor, K252a, a tyrosine receptor kinase (Trk) inhibitor, or anti-TrkB IgG. These findings suggest that the increase in the level of mBDNF and its function during a restricted time window after training are required for the enhancement of memory consolidation by GABA(A) receptor blockade.

| S-EPMC3242303 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data