Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroligin 3 promotes functional recovery of spinal cord injury through coordinating with Sar1a and Hspa8 at synapses

ABSTRACT: The recovery of locomotor function following incomplete spinal cord injury (SCI) primarily relies on the precise reconstruction of synaptic communications between spared corticospinal tract (CST) axons and propriospinal neurons. However, components capable of rebuilding synaptic machinery after injury remain elusive. Here, using RNA-Seq of human umbilical cord-derived MSCs (hUC-MSCs) before and after transplantation in SCI rats, along with in vitro and in vivo functional screenings, we identified Neuroligin 3 (NLGN3) as a spinal cord microenvironment (SCE)-activated cell adhesion molecule (CAM) in hUC-MSCs, promoting MSC-mediated functional recovery of SCI. Importantly, spinal neuron-specific activation of Nlgn3 led to significant functional improvement in SCI rats, resembling the effects of hUC-MSC transplantation. We elucidated the protein interactome of Nlgn3, enriched with proteins involved in synaptic transmission. Specifically, Nlgn3 interacted with synaptic vesicle (SV)-associated proteins, Sar1a and Hspa8, modulating their recruitment at synapses. Remarkably, restoring either of these two proteins in injured spinal neurons improved locomotor recovery of SCI, with further enhancement when combined with Nlgn3. Thus, our results not only reveal the previously unknown therapeutic effect of Nlgn3 in SCI repair but also propose a novel approach for treating SCI by targeting protein complexes centered around Nlgn3. This study also suggests that MSCs can serve as a stem cell platform for identifying innovative therapeutic targets and mechanisms to reestablish corticospinal-spinal relay circuits after SCI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252197 | GEO | 2024/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

hUC-MSC-mediated recovery of subacute spinal cord injury through enhancing the pivotal subunits β3 and γ2 of the GABAA receptor

Project description:We conducted a time-course RNA-seq of spinal cord segments at the lesion site without or with hUC-MSC treatment at subacute phase of SCI to identify genes involved in hUC-MSC-mediated recovery

2022-04-07 | GSE178564 | GEO

Gene expression profiles in the spinal cord below the lesion level and influence of treadmill locomotor training

Project description:Traumatic spinal cord injury (SCI) often leads to loss of locomotor function. Neuroplasticity of spinal circuitry underlies some functional recovery and therefore represents a therapeutic target to improve locomotor function following SCI. However, the cellular and molecular mechanisms mediating neuroplasticity below the lesion level are not fully understood. The present study performed a gene expression profiling in the rat lumbar spinal cord at 1 and 3 weeks after contusive SCI at T9 compared to control rat that received sham injury (laminectomy). The below-level gene expression profiles were compared with those of animals that were subjected to treadmill locomotor training. Rat lumbar spinal cords were taken for the microarray analysis at 1 and 3 weeks after contusive spinal cord injury at the T9 level. Another group of rats received treadmill locomotor training for 3 weeks, and theirs spinal cords were harvested for the microarray. The changes in gene expression after spinal cord injury were analyzed at the two time points. The influence of treadmill locomotor training was evaluated by comparing gene expression profiles between animals with or without treadmill training.

2013-11-27 | E-GEOD-52763 | biostudies-arrayexpress

Gene expression profiles in the spinal cord below the lesion level and influence of treadmill locomotor training

2013-11-27 | GSE52763 | GEO

Molecular responses in skeletal muscles following spinal cord injury and the effect of locomotor training

Project description:Spinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI. The overall objective of this study is to implement genome wide expression profiling of skeletal muscle to define the molecular pathways associated with muscle remodeling after SCI and during locomotor training (TM). We profiled rat soleus of total 36 samples including controls; 3, 8 and 14 days after SCI; 8 and 14 days after SCI with locomotor treadmill training (TM).

2015-06-30 | E-GEOD-45550 | biostudies-arrayexpress

Differential gene expression following SCI in trkB.T1 null

Project description:We asked what genes are significantly differentially regulated in the spinal cord of SCI trkB.T1 WT and trkB.T1 KO mice. TrkB.T1 is upregulated shortly after SCI although the precise mechanisms underyling this upregulation are poorly understood. In the trkB.T1 null, we show less mechanical allodynia and better locomotor recovery following SCI. The microarray studies helped us to elucidate a signaling pathway that is differently regulated in the WT versus KO mice at 1 day after SCI. In this study, we did not examine gene changes within a genotype after SCI. Rather, we examined DGE by genotype at each time point. Spinal cord tissue from WT and KO mice in a sham condition (intact spinal cord) versus 1D, 3D and 7D following SCI was harvested for microarray analyses.

2015-12-07 | E-GEOD-42828 | biostudies-arrayexpress

Molecular responses in skeletal muscles following spinal cord injury and the effect of locomotor training

2015-06-30 | GSE45550 | GEO

The initiating IL-10 production dominates the therapy of mesenchymal stem cell scaffold in spinal cord injury

Project description:spinal cord injury (SCI) is an acute damage to central nevous system, resulting in severe morbidity and permanent disability. Locally implanting scaffold system immobilized mesenchymal stem cellshas been widely proven to promote the locomotor function recovery of SCI rat, but the underlying mechanism remains elusive. Here we constructed a hyaluronic acid scaffold system (HA-MSC) to accelerates human MSC adhesive growth and prolongs the survival time of MSC in the lesion of SCI rats. And the residual MSCs regulate the local immune responses by upregulating anti-inflammatory cytokines. Interestingly, the dramatically increased but transient expression of IL-10 is found secreted by MSCs in the first week. Blocking the function of the initiating produced IL-10 by antibody totally abolishes the neurological and behavioral recovery of SCI rats, indicating a core role of IL-10 in SCI therapy of HA-MSC implantation. Transcriptome analyses indicate that IL-10 selectively promotes the migration and cytokine secretion programs of MSC, which in turn help MSC to exert its anti-inflammatory therapeutic effects. Our findings thus highlight a novel role of IL-10 in regulating MSC migration and cytokine secretion and determine the vital role of IL-10 in the domination of MSC treatment for spinal cord repair.

2024-01-16 | GSE240755 | GEO

Synj 1 modulates functional recovery after motor-incomplete spinal cord injury in male mice carriers of human ApoE4.

Project description:Apolipoprotein E epsilon 4 (ApoE4) is the second most common variant of ApoE, being present in ~14% of population. Clinical reports identify ApoE4 as a genetic risk factor for poor outcomes after traumatic SCI and the spinal cord disease (SCD) cervical myelopathy. To date, there are no interventions to mitigate the potent effects of ApoE4 to reduce recovery of function after SCI/D. Studies in human and mouse brain link ApoE4 to elevated levels of synaptojanin 1 (synj1), a lipid phosphatase that dephosphorylates phosphoinositol 4,5-bisphosphate (PIP2) to inositol 4-monophosphate (PIP1). Synj1 regulates rearrangements of the cytoskeleton and the endocytosis and trafficking of synaptic vesicles. We report here that, as compared to ApoE3 mice, levels of synj1 mRNA and protein were elevated in spinal cords from healthy ApoE4 mice associated with lower PIP2 levels. Using a moderate severity model of contusion SCI in mice, we found that genetic reduction of syn1 improved locomotor function recovery at 14 days after SCI in ApoE4 mice without altering spared white matter. Genetic reduction of synj1 did not alter locomotor recover of ApoE3 mice after SCI. Bulk RNA-sequencing revealed that at 14 days after SCI in ApoE4 mice, genetic reduction of synj1 upregulated genes involved in glutaminergic synaptic transmission just above and below the lesion. Overall, our findings provide evidence for a link between synj1 to poor outcomes after SCI in ApoE4 mice through mechanisms that remain speculative but may include greater function of excitatory glutaminergic synapses.

2023-08-09 | GSE227291 | GEO

Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration

Project description:B-RAF activation in mature corticospinal neurons upregulated a discrete set of transcription factors overlapping with a set induced early in axotomized zebrafish retina ganglion cells which can fully regenerate their axons. Conditional genetic activation of B-RAF promoted robust regeneration and sprouting of corticospinal tract axons after experimental spinal cord injury. Newly sprouting axon collaterals formed synaptic connections, correlating with recovery of skilled motor function. We also found that non-invasive suprathreshold high-frequency repetitive transcranial magnetic stimulation activates the RAF effector MEK and promotes regeneration and sprouting of corticospinal tract axons, dependent on MEK signaling. Our findings demonstrate a central role of neuron-intrinsic RAF–MEK signaling in enhancing the growth capacity of mature corticospinal neurons and propose transcranial magnetic stimulation as a potential therapy for spinal cord injury.

2022-12-31 | GSE201350 | GEO

An aptamer-based bionic spinal cord scaffold elicits robust neurogenesis in situ after spinal cord injury in rats

Project description:Transected spinal cord injury (SCI) results in significant structural disruption of the spinal cord. The reconstruction of neural pathways following SCI faces several key challenges, including inadequate endogenous neural stem cells (NSCs) and poor neurogenesis in natural repair process, and concerns related to the long-term survival of neurons following exogenous transplantation. In the current study, we report an oligonucleotide aptamer drug (Apt19S) which is first proven to recruit endogenous NSCs to the site of injury following SCI, and therefore develop a bionic spinal cord scaffold that can sustainedly release Apt19S and neurotrophin-3 (NT-3) to provide the neurogenic niche with the necessary mechanical properties and support for in situ spinal cord repair. The bionic scaffold successfully recruited a significant number of endogenous NSCs in vivo and established a neurogenic niche that was abundant in NT-3, thereby promoting neuronal differentiation and the formation of neuronal networks Regenerated nerve fibers including 5-hydroxytryptamine-positive nerve fibers and corticospinal tract grew robustly into the injury site and generated synaptic connections with the newborn neurons. Collectively, our findings indicate that our aptamer-based bionic spinal cord scaffold elicits a robust neurogenesis process in situ, breaking the limitations imposed by poor self-repair ability in the adult spinal cord.

2023-10-19 | GSE245409 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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