DIDS protects against neuronal injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12426 | GEO | 2009/08/10
SECONDARY ACCESSION(S): PRJNA113737
REPOSITORIES: GEO
Similar Datasets
Project description:Using long-oligo beadschip arrays, we examined the global gene expression profile in cultured hippocampal slices under the simulated ischemic condition with and without the presence of DIDS . Control-ACSF: cultured hippocampal slices were incubated with ACSF for 2 hours and were analysed on whole-genome expression chips to determine the gene expression profile. This group was used as controls for IS-treated groups and ACSF+DIDS-treated grous. IS: cultured hippocampal slices were treated wtih IS for 2 hours and the gene expression was analyzed and compared with the control group. IS+DIDS: cultured slices were treated with both IS and DIDS for 2 hours and the gene expression profile was determined. Differentially expression genes were identified by comparing with IS group. ACSF+DIDS: cultured slices were incubated with both ACSF and DIDS for 2 hours and gene expression profile was determined. This group was used as a control for IS+DIDS group. ACSF: artificial cerebral spinal fluid DIDS: 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid IS: ischemic solution
2010-05-15 | E-GEOD-12426 | biostudies-arrayexpress
Project description:Primary cardiac myocytes isolated from neonatal Wistar rats were cultured and simulated ischemia/reperfusion injury were conducted on them in the presence or absence of decorin. Decorin is a small leucin-rich proteoglycan, which has a cardiocytoprotective effect. The underlaying mechanism of this cardiocytoprotective phenomenon is unknown, therefore our aim was to investigate the changes in the mRNA expression between the decorin (3nM) treated and vehicle-treated control cells.
2020-12-31 | E-MTAB-9325 | biostudies-arrayexpress
Project description:Background and purposeThe Down syndrome candidate region 1 (DSCR1) gene is located on human chromosome 21 and its protein is over-expressed in brains of Down syndrome individuals. DSCR1 can modulate the activity of calcineurin, a phosphatase abundant in the brain, but its influence on stroke outcome is not clear. We compared stroke outcome in wildtype (WT) and transgenic (DSCR1-TG) mice which over-express isoform 1 of human DSCR1.MethodsTransient cerebral ischemia was produced by occlusion of the middle cerebral artery for 0.5 h. After 23.5 h reperfusion, we assessed neurological impairment, brain infarct and edema volume, leukocyte infiltration and markers of inflammation. Intrinsic resistance to apoptosis following glucose deprivation was also assessed in primary cultures of WT and DSCR1-TG neurons.ResultsIn contrast to WT, DSCR1-TG mice had an improved neurological deficit score, greater grip strength, attenuated infarct volume and brain swelling, and lacked hippocampal lesions after stroke. Expression of mouse DSCR1-1, but not DSCR1-4, mRNA and protein was increased by ischemia in both WT and DSCR1-TG. Brain calcineurin activity was increased to a similar degree after ischemia in each genotype. DSCR1-TG mice had fewer infiltrating neutrophils and activated microglia compared with WT, in association with an attenuated upregulation of several pro-inflammatory genes. Neurons from DSCR1-TG mice were more resistant than WT neurons to apoptotic cell death following 24 h of glucose deprivation.ConclusionsOver-expression of DSCR1 in mice improves outcome following stroke. Mechanisms underlying this protection may involve calcineurin-independent, anti-inflammatory and anti-apoptotic effects mediated by DSCR1 in neurons.
| S-EPMC3483156 | biostudies-literature
Project description:Synaptic dysfunction and degeneration is an early pathological feature of aging and age-related diseases, including Alzheimer's disease (AD). Aging is associated with increased generation and deposition of advanced glycation endproducts (AGEs), resulting from nonenzymatic glycation (or oxidation) proteins and lipids. AGE formation is accelerated in diabetes and AD-affected brain, contributing to cellular perturbation. The extent of AGEs' involvement, if at all, in alterations in synaptic structure and function is currently unknown. Here we analyze the contribution of neuronal receptor of AGEs (RAGE) signaling to AGE-mediated synaptic injury using novel transgenic neuronal RAGE knockout mice specifically targeted to the forebrain and transgenic mice expressing neuronal dominant-negative RAGE (DN-RAGE). Addition of AGEs to brain slices impaired hippocampal long-term potentiation (LTP). Similarly, treatment of hippocampal neurons with AGEs significantly decreases synaptic density. Such detrimental effects are largely reversed by genetic RAGE depletion. Notably, brain slices from mice with neuronal RAGE deficiency or DN-RAGE are resistant to AGE-induced LTP deficit. Further, RAGE deficiency or DN-RAGE blocks AGE-induced activation of p38 signaling. Taken together, these data show that neuronal RAGE functions as a signal transducer for AGE-induced synaptic dysfunction, thereby providing new insights into a mechanism by which the AGEs-RAGE-dependent signaling cascade contributes to synaptic injury via the p38 MAP kinase signal transduction pathway. Thus, RAGE blockade may be a target for development of interventions aimed at preventing the progression of cognitive decline in aging and age-related neurodegenerative diseases.
| S-EPMC4611721 | biostudies-other
Project description:Decorin protects cardiac myocytes against simulated ischemia/reperfusion injury
| PRJEB39277 | ENA
Project description:BackgroundSirtuins (Sirt), a family of nicotinamide adenine nucleotide (NAD) dependent deacetylases, are implicated in energy metabolism and life span. Among the known Sirt isoforms (Sirt1-7), Sirt3 was identified as a stress responsive deacetylase recently shown to play a role in protecting cells under stress conditions. Here, we demonstrated the presence of Sirt3 in neurons, and characterized the role of Sirt3 in neuron survival under NMDA-induced excitotoxicity.Methodology/principal findingsTo induce excitotoxic injury, we exposed primary cultured mouse cortical neurons to NMDA (30 µM). NMDA induced a rapid decrease of cytoplasmic NAD (but not mitochondrial NAD) in neurons through poly (ADP-ribose) polymerase-1 (PARP-1) activation. Mitochondrial Sirt3 was increased following PARP-1 mediated NAD depletion, which was reversed by either inhibition of PARP-1 or exogenous NAD. We found that massive reactive oxygen species (ROS) produced under this NAD depleted condition mediated the increase in mitochondrial Sirt3. By transfecting primary neurons with a Sirt3 overexpressing plasmid or Sirt3 siRNA, we showed that Sirt3 is required for neuroprotection against excitotoxicity.ConclusionsThis study demonstrated for the first time that mitochondrial Sirt3 acts as a prosurvival factor playing an essential role to protect neurons under excitotoxic injury.
| S-EPMC3046953 | biostudies-literature
Project description:Using an in vitro ischemia model (ischemic solution; IS model) that induces penumbral cell death, we examined the effect of 4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid (DIDS) on cell injury/death and underlying molecular mechanisms. Propidium iodide (PI) uptake was used to quantify cell death in organotypic hippocampal slice cultures. A 24-h IS exposure caused a fivefold increase in mean PI fluorescence intensity. DIDS, dose-dependently (1-4000 microM), reduced the IS-induced PI uptake in hippocampal CA1 neurons with an IC(50) of 26 microM. This protective effect of DIDS was reversible and effective even 6 h following the onset of IS treatment. Gene expression profiling studies indicated that among approximately 46,000 transcripts tested, the most significantly up-regulated gene by IS was interleukin-1beta (IL-1beta) which was also the most significantly down-regulated gene when DIDS was added to the IS-treated slices. The addition of a recombinant IL-1 receptor antagonist (100 microg/mL) or neutralizing IL-1beta antibody significantly attenuated the IS-induced cell death, indicating that the up-regulation of IL-1beta with IS treatment contributed to the IS-induced cell death. Toll-like receptor 2 (TLR2), another gene that was significantly up-regulated by IS and suppressed by DIDS, was studied to determine whether it was related to the IL-1beta up-regulation. Indeed, this was the case as the IS-induced IL-1beta up-regulation was abolished in TLR2-/- mouse brain slices. Furthermore, the IS-induced cell death was significantly reduced in TLR2-/- when compared with that in wild-type slices, indicating that TLR2 is functionally upstream of IL-1beta in this IS model. We conclude that (i) IS up-regulates TLR2 expression and augments TLR2 signaling, causing over-expression of IL-1beta which leads to cell death and (ii) DIDS blocks IS-induced neuronal injury, at least partially, by suppressing the TLR2 pathway.
| S-EPMC2782475 | biostudies-literature
Project description:The underlying mechanisms of cerebral ischemia/reperfusion (I/R) injury are unclear. Within this study, we aimed to explore whether p53 inhibition exerts protective effects via the p53/PRAS40/mTOR pathway after stroke and its potential mechanism. Both an in vitro oxygen-glucose deprivation (OGD) model with a primary neuronal culture and in vivo stroke models (dMCAO or MCAO) were used. We found that the infarction size, neuronal apoptosis, and autophagy were less severe in p53 KO mice and p53 KO neurons after cerebral I/R or OGD/R injury. By activating the mTOR pathway, p53 knockdown alleviated cerebral I/R injury both in vitro and in vivo. When PRAS40 was knocked out, the regulatory effects of p53 overexpression or knockdown against stroke disappeared. PRAS40 knockdown could inhibit the activities of the mTOR pathway; moreover, neuronal autophagy and apoptosis were exacerbated by PRAS40 knockdown. To sum up, in this study, we showed p53 inhibition protects against neuronal I/R injury after stroke via the p53/PRAS40/mTOR pathway, which is a novel and pivotal cerebral ischemic injury signaling pathway. The induction of neuronal autophagy and apoptosis by the p53/PRAS40/mTOR pathway may be the potential mechanism of this protective effect.
| S-EPMC8664552 | biostudies-literature
Project description:Background: Acute kidney injury (AKI) is a common clinical event with high morbidity and mortality. We previously demonstrated that injection of cord blood endothelial colony forming cell (ECFC)-derived exosomes, highly enriched in miRNA(miR)-486-5p, prevented ischemic kidney injury in mice. While preclinical models support involvement of several miRs in AKI, the direct effects of miR-486-5p on injury and the kidney transcriptome are unknown. Objective: We studied effects of miR-486-5p in mice with kidney ischemia-reperfusion (IR) injury, and compared the impact of miR-486-5p and ECFC-derived exosomes on the transcriptome of proximal tubules (PTs) and renal endothelial cells. Methods: Adult male mice were subjected to bilateral kidney ischemia (30 min), and injected via tail vein with or without vehicle, miR-486-5p mimic, ECFC-derived exosomes, or scramble miR at the start of reperfusion. Plasma and tissues were collected 24 hrs after reperfusion, and proximal tubular and endothelial cells were isolated for mRNA analysis by RNA-Seq. Results: In mice with kidney IR, injection of miR-486-5p mimic increased levels of miR-486-5p in proximal tubules and endothelial cells, and significantly improved plasma creatinine, histological injury, neutrophil infiltration, and apoptosis, compared to vehicle treatment. MiR-486-5p inhibited expression of phosphatase and tensin homolog (PTEN), and activated AKT. Similar results were observed with exosomes, but scramble miR had no effect. In proximal tubules, miR-486-5p or exosomes reduced expression of several AKI genes (e.g. Lcn2, Havcr1 and Krt20) and caused alterations in apoptotic genes compared to IR alone. In endothelium, miR-486-5p or exosomes caused milder effect than in PTs but still impacting on expression of injury-related genes. Conclusion: MiR-486-5p protects mice against ischemic kidney injury. Both miR-486-5p and exosomes reduce expression of apoptotic genes in PTs and endothelium. The results suggest that systemic delivery of miR-486-5p has therapeutic potential in ischemic AKI.
2023-10-10 | GSE159701 | GEO
Project description:Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg(-1)) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect.
| S-EPMC4278716 | biostudies-literature