Detailed analysis of the murine-aged brain transcriptome [Illumina RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE249499 | GEO | 2024/03/13
REPOSITORIES: GEO
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Project description:In this work, we collected and analyzed two cohorts of young-adult and aged-adult mice brain mRNAs and determined their levels using second- (illumina) and third-generation (Oxford Nanopore) sequencing technologies. We report a transcriptome-wide study of differential transcript usage during brain aging. In addition, we provide the community with a large resource of whole brain transcriptomes and comprehensive analyses that identify widespread diversity of mRNAs during aging.
2024-03-13 | GSE233835 | GEO
Project description:In this work, we collected and analyzed two cohorts of young-adult and aged-adult mice brain mRNAs and determined their levels using second- (illumina) and third-generation (Oxford Nanopore) sequencing technologies. We report a transcriptome-wide study of differential transcript usage during brain aging. In addition, we provide the community with a large resource of whole brain transcriptomes and comprehensive analyses that identify widespread diversity of mRNAs during aging.
2024-03-13 | GSE233836 | GEO
Project description:Aging, which is associated with protein homeostasis defects, is one of the most prominent risk factors for neurodegenerative disorders and the regulation of protein homeostasis is essential for brain health. While several studies have addressed changes in protein abundance due to aging, little is known about differences in protein stability in the mammalian brain proteome. In particular, pre-symptomatic alterations of protein stability might be instrumental for understanding the pathological alterations that occur during neurodegeneration. To explore these alterations, we measured proteome turnover with a pulse-SILAC approach in aged mice from total cortex and cerebellum homogenates and from the respective synaptic-enriched fraction. We compared the stability of young and aged proteomes. Our analyses revealed several differences and the large dataset that we created will serve as a resource for the community to develop approaches that explore these alterations with diagnostic and therapeutic purposes.
2022-06-09 | PXD023994 | Pride
Project description:Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections. Experiment Overall Design: In this study, adult and aged mice were injected intraperitoneal with sterile saline or Escherichia coli LPS (0.33 mg/kg, ~10 µg/mouse; serotype 0127:B8, Sigma). This dosage of LPS was used because it induces a mild transient sickness behavior in young adults. Mice were killed 4 h after saline or LPS injection by CO2 asphyxiation. Blood samples were collected and brains were removed, separated in half at the longitudinal fissure, frozen in liquid nitrogen, and stored (-80°C) until assaying. Total RNA was later isolated from some brain samples for microarray analysis (n=3).
2007-09-07 | E-GEOD-3253 | biostudies-arrayexpress
Project description:Selective isolation of total RNA and then whole genome expression analysis of sprouting neurons in peri-infarct cortex of the adult rat after stroke, compared to adjacent neurons that have not sprouted a new connection, in young adult (2 months) and aged (2 years) animals. Two different fluorescent conjugates of the tracer cholera toxin B (CTb), CTb-Alexa 488 and CTb-Alexa 647 (Molecular Probes), were sequentially injected into peri-infarct cortex at the sites of post-stroke axonal sprouting using a picospritzer pressure injection system. After survival periods of 7 days and 21 days (separate cohorts of animals), CTb-647 was injected exactly within CTb-488 injection site. Seven days after the second tracer injection, laser capture microdissection (LCM) was used to capture ~300 neurons for each cell type. Total RNA was isolated from captured cells and subjected to two rounds of T7 amplification.
2010-11-15 | E-GEOD-24441 | biostudies-arrayexpress
Project description:Immune cells, the most core part of the immune system of the whole body, could rapidly response to the change of environment. Its roles in tissue homeostasis and disease were fairly clear except brain, an immune privilege site. Previous studies had revealed the contribution of microglia, a tissue-resident macrophage, for brain development and neuronal disease. But it was currently unknown whether the other subtypes of immune cells and which of the microglia populations program their function during different stages of development. Here, we analyzed the genes expression pattern of 26,456 immune cells from the whole zebrafish brain during adult and aged stage. Our analysis uncovered the present of lymphocyte in zebrafish brain, and gradually accumulated with aging. In addition, the number of microglia were reduced bute the diversity were increased in aged brain. Collectively, our data provide insights into zebrafish brain immune cells populations that explain the distinct composition of immune cells in adult and aged brain, which might contribute to understanding the roles of immune cells in aging-associated-disease.
2023-01-12 | GSE197673 | GEO
Project description:With advancing age, senescent cells accumulate as they are not efficiently cleared by the immune system anymore. Via a senescence-associated secretory phenotype, chronic senescent cells alter the microenvironment, creating an unfavorable milieu for neurogenesis and neurorepair. Using an innovative and rapid aging model, the African turquoise killifish, we have previously demonstrated a dramatic decline in neurogenic potential of non-glial progenitors with age. Even after traumatic brain injury, progenitor proliferation and neuron production was very low in aged killifish in comparison to young adult killifish, and overall neurorepair was incomplete. In the present study, we validated if the senolytic cocktail dasatinib and quercetin (D+Q) could reboot the neurogenic output by clearing chronic senescent cells from the aged killifish brain to re-create the necessary supportive environment. Our results confirm that the aged killifish telencephalon holds a very high senescent cell burden, which we could diminish by short-term systemic D+Q treatment. As a consequence of D+Q administration, proliferation of non-glial progenitors increased and more new neurons were generated and migrated into the parenchyma after injury. Injury-induced inflammation and glial scarring, a phenomenon only seen in aged killifish, remained unaltered. Senolytic treatment with D+Q might thus hold promise for improving brain function in aged populations, and is especially interesting for reviving the neurogenic potential of an already aged central nervous system.
2023-07-20 | PXD036437 | Pride
Project description:Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45intermediateCD11b+ microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice 14 days after distal middle cerebral artery occlusion (dMCAO) or sham operation and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum in vivo. In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell-cell interactions, such as CXCL10. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after dMCAO. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.
2020-01-31 | GSE142361 | GEO
Project description:<p><strong>BACKGROUND:</strong> The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems, however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients affected the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process, and related functions.</p><p><strong>METHODS AND FINDINGS: </strong>Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. Gut permeability, levels of circulating cytokines and expression of markers of microglia cells were also assessed. FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (<em>Lachnospiraceae</em>, <em>Faecalibaculum</em> and <em>Ruminococcaceae</em>) and disorders of the CNS (<em>Prevotellaceae</em> and <em>Ruminococcaceae</em>) was observed. Finally, microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype, while gut permeability and levels of circulating cytokines remained unaffected.</p><p><strong>CONCLUSIONS:</strong> These results demonstrate a direct effect of the age-associated shifts of the microbiota on protein expression and key functions of the central nervous system. Furthermore, these results additionally highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions in the elderly.</p>
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Project description:It is known that short-term high fat diet consumption leads to significant memory impairments and an exaggerated proinflammatory phenotype in the aged rat brain. To gain a better understanding of the underlying mechanisms driving this cognitive and proinflammatory response, we conducted bulk RNAseq analysis of the hippocampus and amygdala from young adult and aged male rats.
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