Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471628 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7169733_1.fastq.gz | Fastqsanger.gz | |||
| SRR7169733_2.fastq.gz | Fastqsanger.gz | |||
| SRR7169734_1.fastq.gz | Fastqsanger.gz | |||
| SRR7169734_2.fastq.gz | Fastqsanger.gz | |||
| SRR7169735_1.fastq.gz | Fastqsanger.gz |
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Project description:Ischemic stroke is a serious medical condition that leads to neurological symptoms such as loss of motor and cognitive function. Focal cerebral ischemia (FCI) occurs due to interruption of blood supply to the site of injury, leading to the death of brain cells. Cells carrying Neural-glial antigen 2 (NG2) include glial cells serving primarily as olidogendrocyte precursors and a portion of pericytes. NG2 glia proliferate rapidly after ischemia and migrate to the site of injury, participate with astrocytes in glial scar formation, and contribute to the regeneration of the brain tissue. The ability of NG2 glia to differentiate into a different cell type than oligodendrocytes has been described but is still controversial. We therefore isolated NG2 cells and their derivatives labeled with tdTomato red fluorescent protein from the cortex of Rosa26-tdTomato/Cspg4-CreERT2 mice three days after middle cerebral artery occlusion (MCAO). Sham-operated animals were used as healthy controls (CTRL). We aimed to identify NG2 cell types and their derivatives in the cortex of healthy and ischemic mice and determine their incidence as well as characteristic gene expression.
2023-09-21 | E-MTAB-11967 | biostudies-arrayexpress
Project description:NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers an anxiety-like behavior in vivo and induces anxiety-like behavior in a mouse model of chronic social defeat stress.
2020-11-24 | GSE162049 | GEO
Project description:Previous studies have suggested that astrocyte activation in the spinal dorsal horn may play an important role in the development of chronic neuropathic pain; but the mechanisms involved in astrocyte activation and their modulatory effects remain unknown. The inward rectifying potassium channel protein 4.1 (Kir4.1) is the most important background K+ channel in astrocytes. However, how Kir4.1 is regulated and contributes to behavioral hyperalgesia in chronic pain is unknown. In this study, single-cell RNA sequencing analysis indicated that the expression of Kir4.1 and Methyl-CpG-binding protein 2 (MeCP2) were both decreased in spinal astrocytes after chronic constriction injury (CCI) in a mouse model. Conditional knockout of the Kir4.1 channel in spinal astrocytes led to hyperalgesia; and overexpression of the Kir4.1 channel in spinal cord relieved CCI-induced hyperalgesia. Expression of spinal Kir4.1 after CCI was regulated by MeCP2. Electrophysiological recording in spinal slices showed that knockdown of Kir4.1 significantly regulated the excitability of astrocytes and then functionally changed the firing patterns of neurons in dorsal spinal cord. Therefore, targeting spinal Kir4.1 maybe an underlying treatment for hyperalgesia in chronic neuropathic pain.
2022-07-24 | GSE208766 | GEO
Project description:Astrocytes in the retrotrapezoid nucleus (RTN) stimulate breathing in response to CO2/H+, however, it is not clear how these cells detect changes in CO2/H+. Considering Kir4.1/5.1 channels are CO2/H+-sensitive and important for several astrocyte-dependent processes, we consider Kir4.1/5.1 a leading candidate CO2/H+ sensor in RTN astrocytes. To address this, we show that RTN astrocytes express Kir4.1 and Kir5.1 transcripts. We also characterized respiratory function in astrocyte-specific inducible Kir4.1 knockout mice (Kir4.1 cKO); these mice breathe normally under room air conditions but show a blunted ventilatory response to CO2, which could be partly rescued by viral mediated re-expression of Kir4.1 in RTN astrocytes. At the cellular level, astrocytes in slices from astrocyte-specific inducible Kir4.1 knockout mice are less responsive to CO2/H+ and show a diminished capacity for paracrine modulation of respiratory neurons. These results suggest Kir4.1/5.1 channels in RTN astrocytes contribute to respiratory behavior.
2023-12-29 | GSE247704 | GEO
Project description:The inverse effects that dietary sodium and potassium have on blood pressure have been known for some time. High sodium consumption is detrimental, while potassium supplementation is known to be beneficial, and the ratio of sodium/potassium consumption is also very important to consider when determining how these electrolytes affect salt-induced hypertension; however, the mechanisms behind the beneficial effects of potassium are still not yet entirely established. Inwardly rectifying potassium (Kir) channels have been shown to play a major role in potassium transport and homeostasis in the kidney and might contribute to these effects. Here we aimed to examine how different variations in the sodium/potassium ratio affect the development of salt-sensitive hypertension and how channels and transporters in the kidney are altered to accommodate these changes. We hypothesize that these diets will affect the development of salt-sensitive hypertension, and that Kir channels will play a major role in the renal adaptations to varying intakes of potassium
2024-02-24 | GSE255582 | GEO
Project description:Ongoing nociceptive inputs from peripheral tissues and nerve injuries lead to maladaptive alterations in central nervous system, which drive the transition from acute to chronic pain. Although astrocytes act as dynamic and active players in neuropathic pain states, the contribution of astrocytes in upper brain nucleus in this process remains unclear. Here, we revealed that prolonged neuronal inputs induced by periphery injury leads to astrocyte reactive and downregulation of inward rectifying potassium channel protein 4.1 (Kir4.1) in paraventricular thalamus（PVT）. In turn, reactive PVT astrocytes could maintain the hyperexcitability of neurons, and enhanced projections from PVT to medial prefrontal cortex (mPFC) in the chronicity of neuropathic pain. Notably, we identify a neuro-glial interaction mediating pain chronification in PVT, and clarified Kir4.1 channels as a potential therapeutic target for neuropathic pain treatment.
2025-05-20 | GSE297165 | GEO
Project description:Background: As pain persists, it is often accompanied by the development of negative emotional states, such as depression. Approximately 50%-85% of patients with chronic pain experience depressive symptoms. Ventral tegmental area (VTA) γ--aminobutyric acid (GABA) neurons play a crucial role in regulating emotions. VTA GABA neurons can be mainly classified into those expressing somatostatin (SST) and parvalbumin (PV) neurons. The subtypes of VTA GABA neurons exhibit significant heterogeneity, but it remains unclear whether these subtypes mediate different functions in the development of chronic pain and depression. Inward rectifying potassium channel 4.1 (Kir4.1) is an important potassium channel mainly expressed in astrocytes and plays an important role in regulating neural activity. In lipopolysaccharide (LPS)-induced depression, Kir4.1 in lateral habenula (LHb) was upregulated. Lys05 (an inhibitor of Kir4.1) reversed the Kir4.1-driven depression-like phenotype. However, there was no study has reported the changes of Kir4.1 in chronic pain-induced depression or verified the therapeutic effects of Lys05 on it. Methods: We established chronic constriction injury (CCI) model to induce chronic pain in mice, and used the sugar preference test (SPT), tail suspension test (TST), and open field test (OFT) to detect depressive behavior in mice. Lys05 was injected to investigate the effect of Kir4.1 inhibitors on depression caused by chronic neuropathic pain. The adeno-associated virus (AAV) was designed to knockdown or overexpress the expression of Kir4.1 in VTA astrocytes. Using optogenetic manipulations and transgenic mice, specific activation of VTA GABASST neurons or VTA GABAPV neurons was used to explore which types of VTA GABA neurons Kir4.1 has effects on. Patch-clamp recording was applied to explore the effects of Kir4.1 on the excitability of different types of VTA neurons. Results: Lys05 could reverse the depressive behaviors induced by LPS. In detail, mice treated with 10 mg/kg Lys05 showed increased sucrose preference, decreased immobility durations in TST and increased percent center time in OFT. However, Lys05 didn’t show any specific response to depression behavior in CCI-induced depression mice. Then we found Kir4.1 expression decreased in VTA and LHb of CCI-induced depression mice. Next, we found knockdown of Kir4.1 in the VTA resulted mice became depression but with no hyperalgesia. Correspondingly, overexpress Kir4.1 in VTA astrocytes could reverse the chronic pain-induced depression like states. In the patch clamp, when knocked down Kir4.1 in VTA astrocytes, the excitability of dopamine neurons decreased, GABASST neurons increased, but GABAPV neurons did not change significantly. Specifically excitable VTA GABASST neurons could cause depression in mice, while excitable GABAPV neurons did not. Conclusion: Chronic pain decreases the expression of Kir4.1 in VTA astrocytes, which activates GABASST neurons and in turns inhibits DA neurons, then leads depression.
2025-12-01 | GSE283479 | GEO
Project description:Myelinating glia in the auditory system enclose auditory nerve fibers, providing an insulating effect that facilitates rapid transfer of auditory information from the ear to the brain. Here we show that noise exposure at the levels sufficient for inducing hearing loss cause a rapid cellular and molecular response on myelinating glia that precedes neuron degeneration. The response is characterized by inflammatory response, myelin dysmorphology and widespread changes in myelin-related gene expression. Another characteristic was change in expression of the quaking gene (QKI), which encodes a group of RNA binding proteins that are enriched in myelinating glia. Changes in QKI were accompanied by changes in numerous known and potential QKI target genes, including many genes associated with myelination. Our results implicate QKI as a critical early component in the noise response, influencing glia dysfunction that leads to auditory nerve demyelination and, ultimately, sensorineural hearing loss.
2018-04-12 | GSE100365 | GEO
Project description:Nedd4-2 is an E3 ubiquitin ligase in which missense mutation is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2 and an isobaric labeling approach for quantitative comparison of the synaptic membrane proteome, we identified astrocytic channel proteins inwardly rectifying potassium channel 4.1 (Kir4.1) and Connexin43 as upregulated in ubiquitin ligase knockout mice and thus as candidate Nedd4-2 substrates. Kir4.1 and Connexin43 were confirmed as Nedd4-2 substrates by independent methods and their functional role in astrocytes as to modulation of neuronal network activity was established.
2023-11-28 | PXD046450 | Pride
Project description:The ketogenic diet (KD) is an established treatment for patients with medically intractable epilepsy and is chiefly characterized by the production of ketone bodies (KB) such as β-hydroxybutyrate (BHB). However, after more than a century of clinical use, the mechanisms underlying its efficacy remain unclear. While prior investigations have examined the effects of the KD and its metabolic substrates on synaptic transmission, few studies have explored a potential connection between astrocytic ion channels and seizure genesis. One essential function of astrocytes is spatial potassium buffering which influences passive potassium conductance (PPC), and when impaired, can result in neuronal hyperexcitability. In the present study, we demonstrate that the KD can mitigate hippocampal astrogliosis in the Kcna1-null (KO) mouse model of developmental epilepsy. Specifically, we observed a significant increase in GFAP expression in KO mice fed a control diet compared to wild-type (WT) animals, and that the KD prevented this change. Furthermore, we noted a reduction in hippocampal astrocytic PPC in epileptic mice, whereas KD-treated KO animals exhibited nearly normal passive conductance levels. In this regard, we also provide evidence for the role of Kir4.1 channels in mediating astrocytic PPC, and the activation of these inwardly rectifying potassium channels by BHB. To further explore these findings at a molecular level, we conducted bulk RNA-seq analysis which revealed down-regulation of factors linked to hippocampal astrogliosis, notably those involved with neuroinflammation, consistent with earlier reports highlighting the anti-inflammatory effects of the KD and its metabolic substrates such as BHB. Our findings indicate that the KD protects against epilepsy-associated astrogliosis and astrocytic PPC changes, underscoring a novel mechanism of KD action, and the potential functional role of extracellular potassium in neuronal-glial interactions in the epileptic brain.
2025-04-16 | GSE264537 | GEO