Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD22 Blockade Alleviates Anesthesia Surgery-Mediated Cognitive Impairment in Aged Mice

ABSTRACT:

Postoperative cognitive dysfunction (POCD) is a common complication characterized by cognitive decline following surgery, with neuroinflammation serving as a critical pathogenic mechanism. Emerging evidence indicates that CD22, an inhibitory receptor primarily expressed on B cells and microglia, plays a key immunomodulatory role in the central nervous system. This study aims to investigate the role of CD22 in mitigating neuroinflammation and ameliorating POCD. Using a murine model of sterile laparotomy, we observed that surgery-induced cognitive impairment was associated with exacerbated hippocampal inflammation and enhanced microglial activation. In contrast, upregulation or agonism of CD22 signaling significantly reduced the release of pro-inflammatory cytokines, including TNF-α and IL-1β, and suppressed microglial overactivation. Notably, CD22-modulated mice exhibited markedly improved performance in behavioral tests assessing learning and memory compared to control groups. Our findings demonstrate that CD22 activation confers protection against POCD by inhibiting surgery-induced neuroinflammation through the S100a9 signaling pathway. Therefore, targeting the CD22 pathway may represent a promising therapeutic strategy for the prevention or treatment of postoperative cognitive dysfunction.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase

PROVIDER: MTBLS13028 | MetaboLights | 2025-09-24

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	a_MTBLS13028_LC-MS_alternating_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13028_LC-MS_alternating_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13028.txt	Txt

Items per page:

1 - 4 of 4

Similar Datasets

Hippocampal single-cell atlas screening unveils disrupted neuroglial system in postoperative cognitive impairment

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

SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive

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

Complement C3 released from neurotoxic reactive astrocytes impairs learning and memory in the mouse model of postoperative neurodegenerative disorders

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

CCR3 knockdown attenuates prolonged underwater operation-induced cognitive impairment via alleviating microglia-mediated neuroinflammation

Project description:It is important to maintain cognitive integrity during underwater operations, which may also trigger cognitive alterations. Cognitive effect of underwater operations and the underlying mechanism remain elusive. Here, we found a single underwater operation affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, which was accompanied by activation of microglia and upregulation of pro-inflammatory cytokines. RNA-sequencing supported the involvement of neuroinflammation and indicated the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction. Furthermore, the upregulation of pro-inflammatory cytokines was also reversed. Mechanistically, CCR3 knockdown switched the activated microglia from a pro-inflammatory to neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operation-induced cognitive impairment.

2024-05-20 | GSE247651 | GEO

TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis

Project description:Pathological TAR DNA-binding protein-43 (TDP-43) is a defining feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer’s disease (AD). However, the mechanism by which TDP-43 pathology disrupts microglial function and drives neuroinflammation remain unclear. In this study, we demonstrated that cytoplasmic mis-localized TDP-43 exacerbated neuroinflammation, induced cell death, and impaired phagocytic function in microglial cells, primarily through receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis. Pharmacological inhibition of RIPK3 with GSK872 markedly attenuated these pathological effects in vitro. These findings were further corroborated in a murine model with cytoplasmic TDP-43 mis-localization, where GSK872 treatment remarkably alleviated neuroinflammation and restored cognitive deficits. Mechanistically, our findings indicate that the nuclear depletion of TDP-43, resulted from its cytoplasmic mis-localization, impairs its ability to transcriptionally repress the Ripk3 gene, subsequently leading to RIPK3 upregulation and activation of RIPK3-dependent necroptosis. Collectively, our findings establish RIPK3-dependent necroptosis as a critical driver of TDP-43 pathology-mediated neuroinflammation and identified necroptosis as a promising therapeutic target in TDP-43-associated neurodegenerative disorders.

2026-01-04 | GSE315250 | GEO

Postoperative cognitive dysfunction in aged mice after sevoflurane inhalation:crosstalk of gut microbiota, metabolomics, proteomics and protein phosphomics

Project description:General anaesthesia, especially sevoflurane inhalation anaesthesia, is an independent risk factor for postoperative cognitive dysfunction. However, the molecular mechanism by which sevoflurane inhalation alters postoperative cognitive function remains unclear.

2025-04-01 | PXD062444 |

Immunotherapy-related cognitive impairment after CAR T cell therapy in mice

Project description:Persistent central nervous system (CNS) immune dysregulation and consequent dysfunction of multiple neural cell types is central to the neurobiological underpinnings of a cognitive impairment syndrome, colloquially referred to as “brain fog”, that can occur following traditional cancer therapies or certain infections. Immunotherapies have revolutionized cancer care for many tumor types, but the potential long-term cognitive sequelae are incompletely understood. Here, we demonstrate in mouse models that chimeric antigen receptor (CAR) T-cell therapy for both CNS and non-CNS cancers can impair cognitive function and induce a persistent CNS immune response characterized by white matter microglial reactivity, microglial chemokine expression, and elevated cerebrospinal fluid (CSF) cytokines and chemokines. Consequently, oligodendroglial homeostasis and hippocampal neurogenesis are disrupted. Single nucleus sequencing studies of human frontal cortex and subcortical white matter from brain tumor patients with or without previous CAR T-cell therapy confirm reactive states of microglia and oligodendrocytes in patients treated with CAR T cell therapy. In mice, transient microglial depletion or CCR3 chemokine receptor blockade rescues oligodendroglial deficits and cognitive performance in a behavioral test of attention and short-term memory function following CAR T-cell therapy. Taken together, these findings illustrate similar mechanisms underlying immunotherapy-related cognitive impairment (IRCI) and cognitive impairment following traditional cancer therapies and other immune challenges.

2025-02-18 | GSE286221 | GEO

Immunotherapy-related cognitive impairment after CAR T cell therapy in mice [scRNA-seq]

2025-02-18 | GSE287125 | GEO

Intermittent Fasting Reprograms the Brain Proteome to Prevent Synaptic Degeneration and Cognitive Impairment in Vascular Dementia

Project description:Vascular dementia (VaD), driven by chronic cerebral hypoperfusion (CCH), leads to synaptic degeneration and cognitive decline, yet mechanisms linking vascular dysfunction to synaptic loss remain unclear. Intermittent fasting (IF) has emerged as a potential intervention, but its effects on synaptic integrity in VaD are unknown. Using the bilateral common carotid artery stenosis (BCAS) mouse model, we demonstrate that a 16-hour IF regimen preserves cognitive function and cortical synaptic density despite persistent hypoperfusion. Behavioral assays revealed that IF prevented spatial memory deficits in BCAS mice, while electron microscopy confirmed synaptic preservation without altering baseline architecture. Surprisingly, synaptic protein levels remained unchanged, suggesting IF protects synaptic function rather than abundance. Proteomic profiling uncovered dynamic hippocampal adaptations under IF, including upregulation of synaptic stabilizers, enhanced GABAergic signaling, and suppression of neuroinflammatory mediators. IF also attenuated microglial engulfment of synapses, indicating modulation of complement-mediated pruning. Temporal pathway analysis revealed IF’s multi-phase neuroprotection: early synaptic reinforcement, mid-phase metabolic optimization, and late-phase suppression of chronic neuroinflammation. These findings establish IF as a potent modulator of synaptic resilience in VaD, acting through coordinated preservation of synaptic structure, inhibition of inflammatory synapse loss, and metabolic reprogramming. Our results highlight IF’s potential as a non-pharmacological strategy to combat vascular cognitive impairment by targeting the synaptic vulnerability underlying dementia progression.

2025-09-08 | PXD064537 | Pride

Enhanced meningeal lymphatic drainage ameliorates lipopolysaccharide-induced brain injury in aged mice

Project description:Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced by sepsis is considered a potential mechanism of SAE; however, very little is known about the role of the meningeal lymphatic system in SAE. The aged mice with SAE showed a significant decrease in the drainage of OVA-647 into the dCLNs and the coverage of the Lyve-1 in the meningeal lymphatic, indicating that sepsis impaired meningeal lymphatic drainage and morphology. The meningeal lymphatic function of aged mice was more vulnerable to sepsis in comparison to young mice. Sepsis also decreased the protein levels of caspase-3 and PSD95, which was accompanied by reductions in the activity of hippocampal neurons. Microglia were significantly activated in the hippocampus of SAE mice, which was accompanied by an increase in neuroinflammation, as indicated by increases in interleukin-1 beta, interleukin-6 and Iba1 expression. Cognitive function was impaired in aged mice with SAE. However, the injection of AAV1-VEGF-C significantly increased coverage in the lymphatic system and tracer dye uptake in dCLNs, suggesting that AAV1-VEGF-C promotes meningeal lymphangiogenesis and drainage. Furthermore, AAV1-VEGF-C reduced microglial activation and neuroinflammation and improved cognitive dysfunction. Improvement of meningeal lymphatics also reduced sepsis-induced expression of disease-associated genes in aged mice. Pre-existing lymphatic dysfunction by ligating bilateral dCLNs aggravated sepsis-induced neuroinflammation and cognitive impairment.

2023-11-30 | GSE247222 | GEO

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