Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

C1q-dependent clearance of alpha-synuclein allows macrophages to transiently limit enteric synucleinopathy in male mice

ABSTRACT: Here we have utilized the 10x Chromium platform to perform single-cell RNA sequencing on immune cells isolated from mouse duodenum 30 days after inoculation with preformed fibrils of alpha-synuclein or saline (control). This is the first single-cell dataset of the immune landscape during the development of enteric synucleinopathy and thus provides novel insight into the immune response during early stages of enteric neuronal pathology.

ORGANISM(S): Mus musculus

PROVIDER: GSE314156 | GEO | 2026/01/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

C1q-dependent clearance of alpha-synuclein allows macrophages to transiently limit enteric synucleinopathy in male mice

Project description:C1q-dependent clearance of alpha-synuclein allows macrophages to transiently limit enteric synucleinopathy in male mice

| PRJNA1390189 | ENA

Transcriptomic Profiling of Early Synucleinopathy in Rats Induced with Preformed Fibrils

Project description:Transcriptomic Profiling of Early Synucleinopathy in Rats Induced with Preformed Fibrils

| PRJNA1031579 | ENA

Transcriptomic Profiling of Early Synucleinopathy in Rats Induced with Preformed Fibrils

Project description:Examination of early phases of synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development of disease modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized synucleinopathy that recapitulates the pathological features of Parkinson’s disease (PD) and can be used to study synucleinopathy progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons and reactive microglia (major histocompatibility complex-II immunoreactive) peak in the substantia nigra pars compacta (SNpc) months before appreciable neurodegeneration. However, it remains unclear which specific genes are driving these phenotypic changes. To identify transcriptional changes associated with early synucleinopathy, we used laser capture microdissection of the SNpc paired with RNA sequencing (RNASeq). Precision collection of the SNpc allowed for the assessment of differential transcript expression in the nigral dopamine neurons and proximal glia. Transcripts upregulated in early synucleinopathy were mainly associated with an immune response, whereas transcripts downregulated were associated with neurotransmission and the dopamine pathway. A subset of 29 transcripts associated with neurotransmission/vesicular release and the dopamine pathway were verified in a separate cohort of males and females to confirm reproducibility. Within this subset, fluorescent in situ hybridization (FISH) was used to localize decreases in the Syt1 and Slc6a3 transcripts to pSyn inclusion-containing neurons. Identification of transcriptional changes in early synucleinopathy provides insight into the molecular mechanisms driving neurodegeneration.

2023-10-24 | GSE246112 | GEO

Human microglia reduce alpha-synuclein aggregation and are neuroprotective in adult mouse brain

Project description:Microglia, brain-resident immune cells, are involved in pathophysiology of several neurodegenerative diseases, including Parkinson’s disease. Given significant species-specific differences in microglia gene expression, particularly in disease-risk genes, as well as the highly reactive nature of these cells, studying human microglia in a whole brain environment is essential. Here, we established a humanized mouse model by transplanting human induced pluripotent stem cell-derived hematopoietic progenitor cells into the striatum of immunodeficient adult mice and injected human alpha-synuclein preformed fibrils to model Parkinson’s disease pathology. We aimed to create a novel model of Parkinson's disease and studied the response of the human microglia and mouse cells to the preformed fibrils.

2025-09-04 | GSE298706 | GEO

Development of early-stage alpha-synucleinopathy is not governed by myelin status in mice of either sex

Project description:Lewy body disorders are characterized by alpha-synucleinopathic inclusions that tend to develop in neurons extending long, thin, and unmyelinated fibers. It is unknown if this selective vulnerability reflects poor myelination per se. We have observed that preformed fibrils (PFFs) of alpha-synuclein tend to induce pathology in gray matter, even when infused into regions penetrated by white matter bundles. In addition, we found that levels of insoluble, hyperphosphorylated alpha-synuclein correlate inversely with myelin markers in the postmortem amygdala of men—but not women—with Lewy body disease. Thus, we tested if myelin disruption with pharmacologic or genetic tools exacerbates alpha-synucleinopathic lesions in a model of early-stage, limbic Lewy body disease. In genetically outbred CD-1 mice infused with PFFs in the caudal olfactory bulb, the myelin-disruptor cuprizone caused subtle exacerbation of α-synucleinopathy, but without impacting PFF-induced neuron loss or behavior deficits. Furthermore, in C57BL/6J mice heterozygous for myelin basic protein (Mbp+/shi), PFF-induced increases in the insolubility and hyperphosphorylation of alpha-synuclein were not amplified and histological outcomes were not markedly exacerbated. Given our observations of inverse correlations between α-synucleinopathy and myelin markers in the human male amygdala, Lewy body disease may disrupt myelination, rather than poor myelination status regulating the emergence of limbic α-synucleinopathy. This new perspective is reinforced by suppressed expression of select oligodendrocytic markers in the amygdalae of men with Lewy body disease compared to women. Thus, resilient neurons may defy the initial development of Lewy-related pathologies due to properties unrelated to myelination per se.

2025-05-20 | GSE297212 | GEO

Aggregation of α-synuclein scaffolds RNA G-quadruplexes assembly leading to progressive neurodegeneration

Project description:Synucleinopathies are triggered by the aggregation of α-synuclein (αSyn), leading to progressive neurodegeneration. However, the intracellular mechanism of αSyn aggregation remains unclear. Here we show that assembly of RNA G-quadruplexes (rG4s) form scaffolds for αSyn aggregation, contributing to neurodegeneration. Purified αSyn binds rG4s directly through the N-terminus. rG4 itself undergoes phase separation and assembly by Ca2+, accelerating the sol-gel phase transition of αSyn. In αSyn preformed fibrils (PFF)-treated neurons, rG4s assembly composed of synaptic mRNAs co-aggregates with αSyn upon Ca2+ excess influx into cytoplasm, eliciting synaptic dysfunction. Artificial assembly of rG4s using an optogenetic approach evokes αSyn aggregation and neuronal dysfunction. Administration of 5-aminolevulinic acid (5-ALA), a prodrug of protoporphyrin IX (PpIX) that prevents phase separation of rG4s, attenuating αSyn aggregation, neurodegeneration, and progressive motor deficits in PFF-injected synucleinopathy mice. Together, assembly of rG4s due to dysregulation of intracellular Ca2+ homeostasis accelerates αSyn phase transition and aggregation may contribute to pathogenesis of synucleinopathies.

2023-07-18 | GSE234238 | GEO

TNFα-NF-κB activation through pathological α-Synuclein disrupts the BBB and exacerbates axonopathy

Project description:Dysfunction of the blood brain barrier (BBB) is recognized as a key factor in the progression of neurodegenerative diseases, but the detailed mechanisms behind its pathogenesis and impact on neurodegeneration remain elusive. This study aimed to reveal the pathological effects of α-Synuclein (α-Syn), an aggregation protein in Synucleinopathy, on BBB integrity and function, and identify therapeutic targets for α-Syn-related vasculopathy. Using a brain endothelial cell model, we investigated the pathological effect of preformed fibril α-Syn (PFF) on BBB integrity, employing generative adversarial network (GAN) deep learning to analyze pathological changes. We found that PFF activates immune responses, increasing endothelial monolayer permeability via the TNFα-NF-κB pathway. Further in vivo studies with PFF induced α-Synucleinopathy and transgenic animal model (G2-3) revealed that α-Syn aggregation, disrupts the BBB, leading to axonal degeneration that was mitigated by treatment with a non-BBB-penetrating TNFα inhibitor, Etanercept. These findings suggest that targeting brain endothelial TNFα signaling could be a potential therapeutic approach for Synucleinopathy-related NDs.

2025-06-07 | GSE298722 | GEO

Synaptic phosphoproteome modifications and cortical circuit dysfunction are linked to the early-stage progression of alpha-synuclein pathology

Project description:Lewy body inclusions enriched with aggregated forms of the presynaptic protein alpha-synuclein (aSyn) are a hallmark of synucleinopathy diseases such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). To model this pathology, C57 mice were injected in the cortex or striatum with preformed fibrils (PFFs) prepared from mouse aSyn to induce the aggregation of the endogenous mouse protein. Monomeric aSyn was injected as a control. Aggregated aSyn was detected via immunohistochemical staining in the sensorimotor cortex at 1- and 3-months post-injection in PFF-injected mice, but not monomer-injected animals. Phosphoproteomics analysis was carried out on homogenates from the sensorimotor cortex of mice inoculated with PFFs or monomer, 3 months post-injection, and the data are presented here.

2024-11-25 | PXD058091 | Pride

Uptake of alpha-synuclein preformed fibrils is suppressed by inflammation and induces an aberrant phenotype in human microglia

Project description:To detect the microglial mRNA signature whilst phagocytosing alphasynuclein preformed fibrils (αSyn PFFs) with or without inflammatory stimulus, we treated the healthy control microglia with IFNγ (20ng/ml) 28h and αSyn PFFs (0.5µM) 4h

2024-10-22 | GSE277636 | GEO

Molecular and functional features of synucleinopathy-associated astrocytes

Project description:Astrocyte (AC) involvement is a common neuropathological feature in human synucleinopathy-associated neurodegeneration. However, our understanding of the in vivo characteristics of reactive ACs in synucleinopathy remained limited. Here we report the transcriptomic and functional features of a unique synucleinopathy-associated AC (SAA) subtype in a mouse model. SAAs share a convergent transcriptomic state across synucleinopathy-laden brain regions, and are at least partially reliant on microglia for their phenotypic maintenance in vivo. Intravital imaging revealed that an upregulation of the excitatory amino acid transporter 2 (EAAT2) in synucleinopathy-affected ACs is associated with depressed neuronal activities. This is potentially mediated via increased AC glutamate uptake, as pharmacological induction of EAAT2 reproduced the same effect. With cross-species comparative analysis, we showed that the core SAA transcriptomic features are present in human aged and synucleinopathy-affected midbrain ACs, while important distinct characteristics also exist. Collectively, our results uncovered complex reactive AC changes that likely play important adaptive roles in synucleinopathy.

2023-06-30 | GSE205511 | 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