Transgenerational effects of exercise on mouse brain and cognition
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA899092 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR22221119.fastq.gz | Fastqsanger.gz | |||
| SRR22221120.fastq.gz | Fastqsanger.gz | |||
| SRR22221121.fastq.gz | Fastqsanger.gz | |||
| SRR22221122.fastq.gz | Fastqsanger.gz | |||
| SRR22221123.fastq.gz | Fastqsanger.gz |
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Project description:Lifestyle induces long lasting effects on the brain and cognition, with some interventions like stress including transgenerational inheritance on the next generations mediated by epigenetic mechanisms. Physical exercise is one potent intervention driving robust improvements of cognition and brain health, also inducing intergenerational transmission to the litter. However, little is known about whether exercise effects may be transgenerationally transmitted. Here we analyzed the adult hippocampal neurogenesis (AHN) and the behavioral phenotype of sedentary adult male mice of the F2 generation of exercised grandfathers (F0, patrilineal design). Both F1 and F2 were sedentary, while F0 performed a moderate exercise training. We found that the F2 mice from exercised F0 acquired and recalled both spatial and non-spatial information better than F2 from sedentary F0. Contextual fear conditioning resulted not affected, together with no differences in the AHN markers. These results demonstrate that the transgenerational transmission of the effects of exercise on specific cognitive tasks persists after two generations, even though some of the cellular changes induced in F1 disappear in F2, and suggest that moderate exercise training has a longer-lasting effect than previously thought, and this aspect is worth taking into account in public health programs.
2024-06-12 | GSE217487 | GEO
Project description:Intergenerational transmission of the positive effects of physical exercise on brain and cognition
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Project description:Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the adult brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a striking increase in complement cascade inhibitors including clusterin (CLU), which is facilitating the anti-inflammatory effects of runner plasma. Intravenously injected CLU strongly binds to brain endothelial cells reducing their inflammatory gene expression in an acute model of brain inflammation and in Alzheimer’s disease model mice. Cognitively impaired patients participating in structured exercise for 6 months showed improved cognition and higher plasma clusterin levels. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, target the cerebrovasculature and benefit the brain, and are present in humans engaging in exercise.
2021-12-22 | PXD022262 | Pride
Project description:Parental moderate exercise induces positive effects on sedentary litter’s behavior, and on hippocampal gene expression, adult neurogenesis and mitochondrial activation
2019-04-16 | GSE123582 | GEO
Project description:Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered that “runner” plasma, collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a concerted increase in complement cascade inhibitors including clusterin (CLU), a central protein for the anti-inflammatory effects of runner plasma. Intravenously injected CLU strongly binds to brain endothelial cells reducing their inflammatory gene expression in an acute model of brain inflammation and in an Alzheimer’s disease mouse model. Cognitively impaired patients participating in structured exercise for 6 months had higher plasma clusterin levels. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, target the cerebrovasculature and benefit the brain, and are present in humans engaging in exercise.
2021-12-22 | PXD027406 | Pride
Project description:Exercise exerts a wide range of beneficial effects for healthy physiology. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise induced neurochemical changes in the brain. Here, we report on the discovery of a gut brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1 expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut derived interoceptive circuits and provide a microbiome dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut derived signals to the brain may enhance the motivation for exercise.
2023-03-15 | MSV000091494 | MassIVE
Project description:We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the adult brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a striking increase in complement cascade inhibitors including clusterin (CLU), which is facilitating the anti-inflammatory effects of runner plasma. Intravenously injected CLU strongly binds to brain endothelial cells reducing their inflammatory gene expression in an acute model of brain inflammation and in Alzheimer’s disease model mice. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, target the cerebrovasculature and benefit the brain.
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Project description:Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function.
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Project description:Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease. Keywords: expression analysis, transgenerational changes due to vinclozolin
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Project description:This project aims to study the change of brain protein lactylation under treadmill exercise training
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