SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA890228 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21891144_1.fastq.gz | Fastqsanger.gz | |||
| SRR21891144_2.fastq.gz | Fastqsanger.gz | |||
| SRR21891145_1.fastq.gz | Fastqsanger.gz | |||
| SRR21891145_2.fastq.gz | Fastqsanger.gz | |||
| SRR21891146_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Background: Postoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that silent information regulator 1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model. Methods: Exploratory laparotomy was performed in mice aged 12-14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze. Results: SIRT1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration. Conclusion: This study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
2022-12-09 | GSE215410 | GEO
Project description:This study investigates the roles of neurons, microglia, astrocytes, and oligodendrocytes in the pathogenesis of postoperative cognitive impairment, focusing on a dysregulated glia-neuron cycle. We utilized 18-month male C57BL/6 mice to model this condition, conducting single-cell RNA sequencing in the hippocampus to explore the neuroglial interactions and their implications in neuroinflammation, synaptic dysfunction, and myelin loss. This dataset includes transcriptomic profiles aimed at decoding the cellular communication in aged hippocampal cells and assessing the impact of therapeutic interventions on postoperative cognitive decline.
2024-11-14 | GSE267933 | GEO
Project description:BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12-14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
| S-EPMC9685341 | biostudies-literature
Project description:Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1β selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontotemporal dementia (FTD). Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the proximal promoter of IL-1β. Consistent with our findings in mice, selective hypomethylation of IL-1β at two CpG sites are found in normal aging humans and demented patients with tauopathy. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in neurodegenerative diseases. Study of changes related to alterations of SIRT1 levels in microglia of young and aged animals and in models of neurodegenerative dementia
2014-10-01 | E-GEOD-56452 | biostudies-arrayexpress
Project description:Postoperative cognitive dysfunction (POCD) is one of the severe complications inducing low life quality and high mortality after surgery, especially in elderly patients.Here we probed differentially expressed circRNAs using microarray assay in POCD patients, aiming to find potential key circRNAs related to the occurrence of POCD. Subsequently, ten dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) in 10 paired samples. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2020-07-14 | GSE147277 | GEO
Project description:Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1β selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontotemporal dementia (FTD). Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the proximal promoter of IL-1β. Consistent with our findings in mice, selective hypomethylation of IL-1β at two CpG sites are found in normal aging humans and demented patients with tauopathy. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in neurodegenerative diseases.
2014-10-01 | GSE56452 | GEO
Project description:Circular RNAs Expression in Elderly Patients with Postoperative Cognitive Dysfunction
| PRJNA613660 | ENA
Project description:Perioperative neurocognitive disorder (PNDs) can commonly occur after major surgery in at risk patients and its occurrence increases medical healthcare burdens and even mortality. Accumulating evidence points to neuroinflammation being pivotal to the pathogenesis of these conditions. The complement cascade contributes to neuroinflammatory responses in the central nervous system (CNS) and complement C3 has been implicated in the manifestation of cognitive deficits in several neurological conditions. Neurotoxic reactive astrocytes function differently to their non-activated counterparts and release complement components in response to pathological triggers. We observed previously that surgery induces a rapid rise and then fall in cytokines but a more sustained glial activation response that coincided with postoperative cognitive impairment. In this study, we explored the relationship between the expression of complement C3, glial activation, and cognitive deficits. Using a murine model of surgery, we characterized the transcriptional profiles of hippocampal astrocytes after surgery and examined the effects of C3 suppression on the neuroinflammatory response and cognitive performance. There was a delayed but sustained rise in hippocampal C3 of astrocytic in origin after surgery which corresponded with the onset of cognitive decline. Furthermore, the A1 or the neurotoxic phenotype predominated in this postoperative astrocytic activation, and these cells have a distinct transcriptional profile including C3 upregulation. Suppression of C3 inhibited synaptic phagocytosis by microglia and attenuated postoperative cognitive impairment. Therefore, C3 from reactive astrocytes appear central to the development of cognitive dysfunction associated with postoperative neuroinflammation.
2024-03-13 | GSE199318 | GEO
Project description:Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. However, the underlying mechanisms of POCD remain unclear. MicroRNAs (miRNAs) which are involved in the pathogenesis of neurodegenerative diseases, may also affect POCD. To identify the relevant potential mechanisms, in this study, we comprehensively compared the expression profiles of miRNAs in 5 hippocampal tissues from POCD mice and 5 hippocampal tissues from control mice by microarray. A total of 128 miRNAs, whose expression changed significantly, were identified. Four miRNAs were confirmed by quantitative real-time polymerase chain reaction (PCR) in 10 paired samples. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of the deregulated genes. We predicted the potential targets of miRNAs by using bioinformatics methods. In summary, novel miRNAs were identified as potential biomarkers and therapeutic targets for POCD treatment.
2017-02-20 | GSE95070 | GEO
Project description:Sirt1, a NAD-dependent deacetylase, has been shown involved in many complex biological functions. We previously demonstrated that Sirt-1 gain of function is neuroprotective in a model of neurodegenenration. We recently found that Sirt1 loss of function (Sirt1Î mouse) impairs learning, memory, and synaptic plasticity. We used microarray screening to identify potential miRNAs that may be regulated by Sirt1 and ivolved in learning and memory. Total RNA from the hippocampus of SIRT1Î and control mice was extracted and used for microRNA expression level evaluation. Two group experiment, in duplicates. Each sample is compared to a common reference sample, comprised of an equal mixture of all 4 experimental samples.
2010-07-29 | E-GEOD-22530 | biostudies-arrayexpress