GEO accession GSE269061 is currently private and is scheduled to be released on Aug 04, 2026.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1120039 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR29280363.fastq.gz | Fastqsanger.gz | |||
| SRR29280364.fastq.gz | Fastqsanger.gz | |||
| SRR29280366.fastq.gz | Fastqsanger.gz | |||
| SRR29280367.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Blood factors transfer the benefits of exercise to the aged brain, independent of physical activity. Here we show that liver-derived exercise factor glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer’s-related memory loss by targeting brain vasculature. GPLD1 has potential to cleave over 100 putative GPI-anchored proteins, necessitating identification of downstream targets that mediate cognitive rejuvenation for translational application. We identified GPI-anchored tissue-nonspecific alkaline phosphatase (TNAP) on brain vasculature as a GPLD1 substrate. Mimicking the age-related increase in cerebrovascular TNAP impaired blood-brain transport and cognition in young mice and mitigated Gpld1-induced cognitive benefits in aged mice. Inhibiting TNAP recapitulated benefits of GPLD1 in old age, restoring youthful hippocampal transcriptional signatures and rescuing cognition. In an Alzheimer’s disease model, increasing GPLD1, or inhibiting TNAP, ameliorated Ab pathology and improved cognitive deficits. We thus identify brain vasculature as a mediator of the cognitive benefits of a liver-to-brain exercise axis.
2026-02-09 | GSE304483 | GEO
Project description:Blood factors transfer the benefits of exercise to the aged brain. However, mechanisms to restore cognition and the translational application to neurodegenerative disorders are unknown. Here we show that liver-derived exercise factor glycosylphosphatidylinositol (GPI)-specific phospholipase D1(Gpld1)–a GPI-degrading enzyme–reverses aging and Alzheimer’s-related memory loss by targeting brain vasculature. Increasing Gpld1 rejuvenated transcriptional hippocampal aging signatures at a single cell level and rescued memory in aged mice. Mechanistically, we identified GPI-anchored tissue-nonspecific alkaline phosphatase (TNAP) on brain vasculature as a GPLD1 substrate. Mimicking an age-related increase in cerebrovascular TNAP impaired memory in young mice and mitigated Gpld1-mediated cognitive benefits in aged mice. Inhibiting TNAP activity recapitulated the benefits of Gpld1 in old age. In an Alzheimer’s disease model, increasing Gpld1, or inhibiting TNAP, ameliorated A pathology and improved cognitive deficits. Collectively, our data identify cerebrovasculature as a gatekeeper of the restorative cognitive benefits of a liver-to-brain exercise axis.
2026-03-11 | GSE269061 | GEO
Project description:LIVER EXERCISE FACTOR REVERSES AGING- AND ALZHEIMER’S-RELATED MEMORY LOSS BY TARGETING BRAIN VASCULATURE
| PRJNA1301371 | ENA
Project description:Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training. Keywords: resistance exercise, muscle, aging
2007-07-16 | GSE8479 | 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 “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: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: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.
2021-09-01 | GSE164401 | GEO
Project description:We utilized an unbiased RNA-sequencing approach to uncover genes in the dorsal hippocampus that are differentially expressed under conditions where exercise benefits are maintained throughout sedentary delay periods and enable the formation of long-term memory and synaptic plasticity. Engagement in different exercise parameters resulted in a diverse transcriptional profile as defined by differences in the number, pattern, and type of genes up and down-regulated. To identify genes that play a critical role in cognitive enhancement, we next focused our attention on exercise groups that enable robust long-term memory formation under inadequate subthreshold acquisition sessions of the hippocampus-dependent object location memory task. By intersecting up regulated genes when exercise facilitated learning, we identify potential regulators of learning and targets for memory enhancement. We identify a gene coding for a type 1 membrane receptor and kinase for the TGF-β family of signaling molecules, Acvr1c as one of few genes showing upregulation in conditions where exercise enabled the formation of long-term memory, indicating a gate-type role for Acvr1c in memory consolidation. In addition to overall gene expression levels, we identify potential regulators upstream of gene targets within the window for cognitive enhancement. Additionally, we use three complementary analyses to examine the mechanisms responsible for maintaining the ‘molecular memory window’ for exercise utilizing up regulated differentially expressed genes compared to sedentary controls. These analyses include: gene coexpression network analysis to identify potential hub genes for each exercise condition, predicted pathways altered by exercise, and gene ontology enrichment analysis of cellular components altered by exercise. Together, results identify Acvr1c as one of few genes up regulated only under conditions where exercise enabled the formation of long-term memory and synaptic plasticity, suggesting a role for Acvr1c in facilitation of memory consolidation. Follow up experiments manipulating ACVR1C function, find that it serves as an essential bidirectional regulator of long-term memory formation capable of alleviating impairments in hippocampus-dependent memory and synaptic plasticity associated with age and Alzheimer’s Disease.
2022-12-01 | GSE208615 | GEO
Project description:Although exercise improves cognition, the specific molecules responsible for these beneficial effects remain unclear. Here, we propose that the myokine Serpina1e acts as a molecular mediator for these effects. Using an in vivo myokine-labeling mouse model, we confirmed that the Serpina1 family of proteins are increased after 4 weeks of aerobic exercise. Systemic delivery of recombinant Serpina1e enhanced hippocampal memory formation, promoted hippocampal neurogenesis, and elevated BDNF levels. Moreover, plasma Serpina1e can cross the blood–cerebral spinal fluid (CSF) barrier and blood–brain barrier to reach the brain, thereby influencing hippocampal function. In vivo Serpina1e infusion also induced cognitive enhancement. Our findings suggest that Serpina1e is a myokine that migrates to the hippocampus and mediates exercise-induced memory enhancement by triggering neurotrophic growth signaling. This molecular mechanism underlying the beneficial effects of exercise on cognitive function may have implications for the development of therapeutic interventions for alleviating cognitive disorders.
2026-06-15 | PXD055604 | Pride
Project description:Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer’s disease (AD) risk, but its functions are not fully understood. Here, we found that medial prefrontal cortex (mPFC) injection with chondroitinase ABC (ChABC) to remodel ECM reverses short-term memory loss and reduces Aβ deposition in 5xFAD mice. ECM remodeling also reactivates astrocytes, untangles aggrecan’s entanglement with amyloid-beta (Aβ) plaques, and encourages astrocyte recruitment to the surrounding plaques. ECM remodeling promotes astrocyte phagocytosis of Aβ plaque by activating the astrocyte phagocytosis receptor mertk and astrocytic vesicle circulation. Importantly, ECM remodeling enhances the autophagy-lysosome pathway in astrocytes to mediate Aβ clearance and alleviate AD pathology. Our work thus discovers a cellular mechanism to remodel the ECM to active astrocyte autophagic lysosomal pathway alleviation AD pathology. It may represent a potential therapeutic strategy and serve as a hallmark for treating AD.
2024-10-17 | PXD046784 | Pride