14,466 results match your criteria cortical astrocytes

Recovery of Depleted miR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons.

Front Cell Dev Biol 2021 23;9:634355. Epub 2021 Apr 23.

Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.

Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Read More

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Cell-Type-Specific Gene Modules Related to the Regional Homogeneity of Spontaneous Brain Activity and Their Associations With Common Brain Disorders.

Front Neurosci 2021 20;15:639527. Epub 2021 Apr 20.

Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.

Mapping gene expression profiles to neuroimaging phenotypes in the same anatomical space provides opportunities to discover molecular substrates for human brain functional properties. Here, we aimed to identify cell-type-specific gene modules associated with the regional homogeneity (ReHo) of spontaneous brain activity and their associations with brain disorders. Fourteen gene modules were consistently associated with ReHo in the three datasets, five of which showed cell-type-specific expression (one neuron-endothelial module, one neuron module, one astrocyte module and two microglial modules) in two independent cell series of the human cerebral cortex. Read More

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PET Imaging of Peripheral Benzodiazepine Receptor Standard Uptake Value Increases After Controlled Cortical Impact, a Rodent Model of Traumatic Brain Injury.

ASN Neuro 2021 Jan-Dec;13:17590914211014135

Department of Pediatric Surgery, University of Texas Medical School at Houston, Texas, United States.

Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Read More

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MicroRNA-34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis.

Neuropathol Appl Neurobiol 2021 May 3. Epub 2021 May 3.

Department of (Neuro) Pathology, UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.

Aims: Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signalling pathway. Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers in the brain. We previously reported microRNA-34a (miR-34a) among the most up-regulated miRs in tubers. Read More

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Isolation of Adult Human Astrocyte Populations from Fresh-frozen Cortex using Fluorescence-Activated Nuclei Sorting.

J Vis Exp 2021 Apr 16(170). Epub 2021 Apr 16.

Department of Pathology, Icahn School of Medicine at Mount Sinai; Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai;

The complexity of human astrocytes remains poorly defined in primary human tissue, requiring better tools for their isolation and molecular characterization. Fluorescence-activated nuclei sorting (FANS) can be used to successfully isolate and study human neuronal nuclei (NeuN+) populations from frozen archival tissue, thereby avoiding problems associated with handling fresh tissue. However, efforts to similarly isolate astroglia from the non-neuronal (NeuN-) element are lacking. Read More

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Molecular Basis of GABA Hypofunction in Adolescent Schizophrenia-Like Animals.

Neural Plast 2021 15;2021:9983438. Epub 2021 Apr 15.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Schizophrenia is a neurodevelopmental disorder that NMDA receptor (NMDAR) hypofunction appears centrally involved. Schizophrenia typically emerges in adolescence or early adulthood. Electrophysiological and several neurochemical changes have linked the GABA deficits to abnormal behaviors induced by NMDAR hypofunction. Read More

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The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation.

Int J Mol Sci 2021 Apr 16;22(8). Epub 2021 Apr 16.

Department of Cancer Biology, University of Cincinnati College Medicine, Cincinnati, OH 45267, USA.

Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. TSC affects multiple organs including the brain. The neurologic manifestation is characterized by cortical tubers, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA) in brain. Read More

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Ischemia-Reperfusion under Hyperthermia Increases Heme Oxygenase-1 in Pyramidal Neurons and Astrocytes with Accelerating Neuronal Loss in Gerbil Hippocampus.

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Gangwon, Korea.

It has been studied that the damage or death of neurons in the hippocampus is different according to hippocampal subregions, cornu ammonis 1-3 (CA1-3), after transient ischemia in the forebrain, showing that pyramidal neurons located in the subfield CA1 (CA1) are most vulnerable to this ischemia. Hyperthermia is a proven risk factor for brain ischemia and can develop more severe and extensive brain damage related with mortality rate. It is well known that heme oxygenase-1 (HO-1) activity and expression is increased by various stimuli in the brain, including hyperthermia. Read More

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Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Aix Marseille University, Inserm, MMG, Marseille Medical Genetics, 13385 Marseille, France.

Mutations in the X-linked gene are responsible for Rett syndrome (RTT), a severe neurological disorder. MECP2 is a transcriptional modulator that finely regulates the expression of many genes, specifically in the central nervous system. Several studies have functionally linked the loss of MECP2 in astrocytes to the appearance and progression of the RTT phenotype in a non-cell autonomous manner and mechanisms are still unknown. Read More

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Astrocytic IGF-IRs induce adenosine-mediated inhibitory down regulation and improve sensory discrimination.

J Neurosci 2021 Apr 19. Epub 2021 Apr 19.

Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, 28029, Spain

Insulin-like growth factor-I (IGF-I) signalling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signalling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTP, here called LTP) of the postsynaptic potentials that is caused by a long-term depression (LTD) of inhibitory synaptic transmission in mice. Read More

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The Contribution of Astrocyte and Neuronal Panx1 to Seizures Is Model and Brain Region Dependent.

ASN Neuro 2021 Jan-Dec;13:17590914211007273

Department of Cell Biology & Anatomy, New York Medical College, Valhalla, New York, United States.

Pannexin1 (Panx1) is an ATP release channel expressed in neurons and astrocytes that plays important roles in CNS physiology and pathology. Evidence for the involvement of Panx1 in seizures includes the reduction of epileptiform activity and ictal discharges following Panx1 channel blockade or deletion. However, very little is known about the relative contribution of astrocyte and neuronal Panx1 channels to hyperexcitability. Read More

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Single intracerebroventricular progranulin injection adversely affects the blood-brain barrier in experimental traumatic brain injury.

J Neurochem 2021 Apr 26. Epub 2021 Apr 26.

Department of Anesthesiology, University Medical Center Johannes Gutenberg-University, Mainz, Germany.

Progranulin (PGRN) is a neurotrophic and anti-inflammatory factor with protective effects in animal models of ischemic stroke, subarachnoid hemorrhage and traumatic brain injury (TBI). Administration of recombinant (r) PGRN prevents exaggerated brain pathology after TBI in Grn-deficient mice suggesting that local injection of rPGRN provides therapeutic benefit in the acute phase of TBI. To test this hypothesis, we subjected adult male C57Bl/6N mice to the controlled cortical impact model of TBI, administered a single dose of rPGRN intracerebroventricularly (ICV) shortly before the injury, and examined behavioral and biological effects up to 5 days post injury (dpi). Read More

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Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons.

J Cereb Blood Flow Metab 2021 Apr 25:271678X211010355. Epub 2021 Apr 25.

Graduate School of Informatics and Engineering, University of Electro-Communications, Tokyo, Japan.

A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e. Read More

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Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration.

J Lipid Res 2021 Apr 21:100079. Epub 2021 Apr 21.

Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University, St. Louis, MO 63110, USA; Departments of Cell Biology & Physiology, Washington University, St. Louis, MO 63110, USA. Electronic address:

Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders. However, the mechanistic links between ether phospholipids, blood pressure, and neurodegeneration are not fully understood. Read More

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S1P-Gα signaling inhibits astrocytic glutamate uptake and mitochondrial oxygen consumption.

eNeuro 2021 Apr 23. Epub 2021 Apr 23.

Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA 92037

Glutamate is the principal excitatory neurotransmitter in the human brain. Following neurotransmission, astrocytes remove excess extracellular glutamate to prevent neurotoxicity. Glutamate neurotoxicity has been reported in multiple neurological diseases including multiple sclerosis (), representing a shared neurodegenerative mechanism. Read More

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Developmental role of adenosine kinase in the cerebellum.

eNeuro 2021 Apr 14. Epub 2021 Apr 14.

Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA

Adenosine acts as a neuromodulator and metabolic regulator of the brain through receptor dependent and independent mechanisms. In the brain, adenosine is tightly controlled through its metabolic enzyme adenosine kinase, which exists in a cytoplasmic (ADK-S) and nuclear (ADK-L) isoform. We recently discovered that ADK-L contributes to adult hippocampal neurogenesis regulation. Read More

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Calcium-dependent cytosolic phospholipase A activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.

Mol Neurodegener 2021 04 16;16(1):26. Epub 2021 Apr 16.

Departments of Medicine and Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer's disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known. Read More

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Region-specific changes in aquaporin 4 induced by hyperglycemia underlie the differences in cell swelling in the cortex and striatum after cerebral ischemia-reperfusion.

Neurosci Lett 2021 May 15;754:135885. Epub 2021 Apr 15.

Department of Pathology, School of Basic Medical Science, Ningxia Medical University, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Yinchuan, Ningxia, 750004, China. Electronic address:

Brain edema is a major cause of death in patients who suffer an ischemic stroke. Diabetes has been shown to aggravate brain edema after cerebral ischemia-reperfusion, but few studies have focused on the heterogeneity of this response across different brain regions. Aquaporin 4 plays an important role in the formation and regression of brain edema. Read More

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The effect of female sex hormones on Hsp27 phosphorylation and histological changes in prefrontal cortex after tMCAO.

Pathol Res Pract 2021 Mar 24;221:153415. Epub 2021 Mar 24.

Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. Electronic address:

Background: Female sex hormones are protective factors against many neurological disorders such as brain ischemia. Heat shock protein like HSP27 is activated after tissue injury. The main purpose of the present study is to determine the effect of a combined estrogen / progesterone cocktail on the morphology of astrocytes, neurons and Hsp27 phosphorylation after cerebral ischemia. Read More

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Adrenergic inhibition facilitates normalization of extracellular potassium after cortical spreading depolarization.

Sci Rep 2021 Apr 14;11(1):8150. Epub 2021 Apr 14.

Laboratory for Neuron-Glia Circuitry, RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan.

Cortical spreading depolarization (CSD) is a propagating wave of tissue depolarization characterized by a large increase of extracellular potassium concentration and prolonged subsequent electrical silencing of neurons. Waves of CSD arise spontaneously in various acute neurological settings, including migraine aura and ischemic stroke. Recently, we have reported that pan-inhibition of adrenergic receptors (AdRs) facilitates the normalization of extracellular potassium after acute photothrombotic stroke in mice. Read More

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Cracking the Codes of Cortical Glial Progenitors: Evidence for the Common Lineage of Astrocytes and Oligodendrocytes.

Neurosci Bull 2021 Apr 13;37(4):437-439. Epub 2021 Apr 13.

Institute of Life Sciences, College of Life and Environmental Sciences, College of Basic Medical Science, Hangzhou Normal University, Hangzhou, 311121, China.

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Conversion of Reactive Astrocytes to Induced Neurons Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke.

Front Aging Neurosci 2021 26;13:612856. Epub 2021 Mar 26.

Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, United States.

The master neuronal transcription factor NeuroD1 can directly reprogram astrocytes into induced neurons (iNeurons) after stroke. Using viral vectors to drive ectopic ND1 expression in gliotic astrocytes after brain injury presents an autologous form of cell therapy for neurodegenerative disease. Cultured astrocytes transfected with ND1 exhibited reduced proliferation and adopted neuronal morphology within 2-3 weeks later, expressed neuronal/synaptic markers, and extended processes. Read More

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Inflammatory Foreign Body Response Induced by Neuro-Implants in Rat Cortices Depleted of Resident Microglia by a CSF1R Inhibitor and Its Implications.

Front Neurosci 2021 26;15:646914. Epub 2021 Mar 26.

Department of Neurobiology, The Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem, Israel.

Inflammatory encapsulation of implanted cortical-neuro-probes [the foreign body response (FBR)] severely limits their use in basic brain research and in clinical applications. A better understanding of the inflammatory FBR is needed to effectively mitigate these critical limitations. Combining the use of the brain permeant colony stimulating factor 1 receptor inhibitor PLX5622 and a perforated polyimide-based multielectrode array platform (PPMP) that can be sectioned along with the surrounding tissue, we examined the contribution of microglia to the formation of inflammatory FBR. Read More

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OTULIN is a new target of EA treatment in the alleviation of brain injury and glial cell activation via suppression of the NF-κB signalling pathway in acute ischaemic stroke rats.

Mol Med 2021 04 9;27(1):37. Epub 2021 Apr 9.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Objective: Ovarian tumour domain deubiquitinase with linear linkage specificity (OTULIN) is a potent negative regulator of the nuclear factor-κB (NF-κB) signalling pathway, and it plays a strong neuroprotective role following acute ischemic stroke. Electroacupuncture (EA) is an effective adjuvant treatment for reducing brain injury and neuroinflammation via the inhibition of NF-κB p65 nuclear translocation, but the underlying mechanism is not clear. The present study investigated whether OTULIN was necessary for EA to mitigate brain injury and glial cell activation in a transient middle cerebral artery occlusion (tMCAO) model in rats. Read More

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Transient Astrocytic Gq Signaling Underlies Remote Memory Enhancement.

Front Neural Circuits 2021 22;15:658343. Epub 2021 Mar 22.

Laboratory for Neuron-Glia Circuitry, RIKEN Center for Brain Science, Wako, Japan.

Astrocytes elicit transient Ca elevations induced by G protein-coupled receptors (GPCRs), yet their role remains unknown. To address this, transgenic mice with astrocytic expression of the optogenetic Gq-type GPCR, Optoα1AR, were established, in which transient Ca elevations similar to those in wild type mice were induced by brief blue light illumination. Activation of cortical astrocytes resulted in an adenosine A1 receptor-dependent inhibition of neuronal activity. Read More

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Neuroinflammation is highest in areas of disease progression in semantic dementia.

Brain 2021 Apr 6. Epub 2021 Apr 6.

Nantz National Alzheimer Center, Stanley H. Appel Department of Neurology, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, USA.

Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation. Read More

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Establishment of Long-Term Primary Cortical Neuronal Cultures From Neonatal Opossum .

Front Cell Neurosci 2021 18;15:661492. Epub 2021 Mar 18.

Laboratory for Molecular Neurobiology, Department of Biotechnology, University of Rijeka, Rijeka, Croatia.

Primary dissociated neuronal cultures have become a standard model for studying central nervous system (CNS) development. Such cultures are predominantly prepared from the hippocampus or cortex of rodents (mice and rats), while other mammals are less used. Here, we describe the establishment and extensive characterization of the primary dissociated neuronal cultures derived from the cortex of the gray South American short-tailed opossums, . Read More

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Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids.

Front Cell Neurosci 2021 17;15:631548. Epub 2021 Mar 17.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.

Human stem cell derived brain organoids are increasingly gaining attention as an ideal model system for investigating neurological diseases, particularly those that involve myelination defects. However, current protocols for generating brain organoids with sufficiently mature oligodendrocytes that deposit myelin on endogenously produced neurons are lengthy and complicated. Taking advantage of a human pluripotent stem cell line that reports on SOX10 expression, we developed a protocol that involves a 42 day exposure of neuroectoderm-derived organoids to a cocktail of growth factors and small molecules that collectively foster oligodendrocyte specification and survival. Read More

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Improved l-Type amino acid transporter 1 (LAT1)-mediated delivery of anti-inflammatory drugs into astrocytes and microglia with reduced prostaglandin production.

Int J Pharm 2021 Apr 1;601:120565. Epub 2021 Apr 1.

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Electronic address:

Non-steroidal anti-inflammatory drugs (NSAIDs) can have protective effects in the brain by inhibition of cyclooxygenases (COX). However, the delivery into the brain across the blood-brain barrier (BBB) and particularly into the brain parenchymal cells is hindered. Therefore, in the present study, we developed four l-type amino acid transporter 1 (LAT1)-utilizing prodrugs of flurbiprofen, ibuprofen, naproxen, and ketoprofen, since LAT1 is expressed on both, the BBB endothelial cells as well as parenchymal cells. Read More

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Astrocyte Ca Waves and Subsequent Non-Synchronized Ca Oscillations Coincide with Arteriole Diameter Changes in Response to Spreading Depolarization.

Int J Mol Sci 2021 Mar 26;22(7). Epub 2021 Mar 26.

Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Korányi fasor 9, 6720 Szeged, Hungary.

Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca oscillations in the mouse somatosensory cortex. Read More

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