Similar Datasets
Project description:Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype
2023-02-08 | GSE197015 | GEO
Project description:Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype
2023-02-08 | GSE224494 | GEO
Project description:Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype
2023-02-08 | GSE190452 | GEO
Project description:Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype
2023-02-08 | GSE190451 | GEO
Project description:Glial reaction is a common feature of neurodegenerative diseases. Recent studies have suggested that reactive astrocytes gain neurotoxic properties, but exactly how reactive astrocytes contribute to neurotoxicity remains to be determined. Here, we identify lipocalin 2 (lcn2) as an inducible factor that is secreted by reactive astrocytes and that is selectively toxic to neurons. We show that lcn2 is induced in reactive astrocytes in transgenic rats with neuronal expression of mutant human TAR DNA-binding protein 43 (TDP-43) or RNA-binding protein fused in sarcoma (FUS). Therefore, lcn2 is induced in activated astrocytes in response to neurodegeneration, but its induction is independent of TDP-43 or FUS expression in astrocytes. We found that synthetic lcn2 is cytotoxic to primary neurons in a dose-dependent manner, but is innocuous to astrocytes, microglia, and oligodendrocytes. Lcn2 toxicity is increased in neurons that express a disease gene, such as mutant FUS or TDP-43. Conditioned medium from rat brain slice cultures with neuronal expression of mutant TDP-43 contains abundant lcn2 and is toxic to primary neurons as well as neurons in cultured brain slice from WT rats. Partial depletion of lcn2 by immunoprecipitation reduced conditioned medium-mediated neurotoxicity. Our data indicate that reactive astrocytes secrete lcn2, which is a potent neurotoxic mediator.
| S-EPMC3593910 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-02-12 | GSE130119 | GEO
Project description:Reprogramming brain-resident glial cells into clinically relevant induced neurons (iNs) is an emerging strategy toward replacing lost neurons and restoring lost brain functions. A fundamental question is now whether iNs can promote functional recovery in pathological contexts. We addressed this question in the context of therapy-resistant mesial temporal lobe epilepsy (MTLE), which is associated with hippocampal seizures and degeneration of hippocampal GABAergic interneurons. Using a MTLE mouse model, we show that retrovirus-driven expression of Ascl1 and Dlx2 in reactive hippocampal glia in situ, or in cortical astroglia grafted in the epileptic hippocampus, causes efficient reprogramming into iNs exhibiting hallmarks of interneurons. These induced interneurons functionally integrate into epileptic networks and establish GABAergic synapses onto dentate granule cells. MTLE mice with GABAergic iNs show a significant reduction in both the number and cumulative duration of spontaneous recurrent hippocampal seizures. Thus glia-to-neuron reprogramming is a potential disease-modifying strategy to reduce seizures in therapy-resistant epilepsy.
| S-EPMC8657801 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-07-11 | GSE236929 | GEO
Project description:Astrocytes have emerged for playing important roles in brain tissue repair; however, the underlying mechanisms remain poorly understood. We show that acute injury and blood-brain barrier disruption trigger the formation of a prominent mitochondrial-enriched compartment in astrocytic endfeet, which enables vascular remodeling. Integrated imaging approaches revealed that this mitochondrial clustering is part of an adaptive response regulated by fusion dynamics. Astrocyte-specific conditional deletion of Mitofusin 2 (Mfn2) suppressed perivascular mitochondrial clustering and disrupted mitochondria-endoplasmic reticulum (ER) contact sites. Functionally, two-photon imaging experiments showed that these structural changes were mirrored by impaired mitochondrial Ca2+ uptake leading to abnormal cytosolic transients within endfeet in vivo. At the tissue level, a compromised vascular complexity in the lesioned area was restored by boosting mitochondrial-ER perivascular tethering in MFN2-deficient astrocytes. These data unmask a crucial role for mitochondrial dynamics in coordinating astrocytic local domains and have important implications for repairing the injured brain.
| S-EPMC7139200 | biostudies-literature
Project description:PURPOSE:To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction. METHODS:Electroencephalography (EEG), electromyography (EMG), and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1-300 Hz) were stored 24 h a day for more than 12 days. Low frequency stimulation (LFS) (3 Hz, square wave, biphasic, 100 ?s, 400 ?A) was applied to the ventral hippocampal commissure (VHC) in alternating 5 min cycles (on or off) 24 h a day for a period of 4 days. RESULTS:LFS (3 Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p < 0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state ("on" vs. "off"). CONCLUSION:LFS applied at a frequency of 3 Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action.
| S-EPMC3569726 | biostudies-literature