Slow degradation in phagocytic astrocytes can be enhanced by lysosomal acidification.

Abstract:

:Inefficient lysosomal degradation is central in the development of various brain disorders, but the underlying mechanisms and the involvement of different cell types remains elusive. We have previously shown that astrocytes effectively engulf dead cells, but then store, rather than degrade the ingested material. In the present study we identify reasons for the slow digestion and ways to accelerate degradation in primary astrocytes. Our results show that actin-rings surround the phagosomes for long periods of time, which physically inhibit the phago-lysosome fusion. Furthermore, astrocytes express high levels of Rab27a, a protein known to reduce the acidity of lysosomes by Nox2 recruitment, in order to preserve antigens for presentation. We found that Nox2 colocalizes with the ingested material, indicating that it may influence antigen processing also in astrocytes, as they express MHC class II. By inducing long-time acidification of astrocytic lysosomes using acidic nanoparticles, we could increase the digestion of astrocyte-ingested, dead cells. The degradation was, however, normalized over time, indicating that inhibitory pathways are up-regulated in response to the enhanced acidification. GLIA 2015;63:1997-2009.

journal_name

Glia

journal_title

Glia

authors

Lööv C,Mitchell CH,Simonsson M,Erlandsson A

doi

10.1002/glia.22873

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1997-2009

issue

11

eissn

0894-1491

issn

1098-1136

journal_volume

63

pub_type

杂志文章

相关文献

GLIA文献大全
  • Purinergic P2Y receptors on astrocytes are directly coupled to phospholipase A2.

    abstract::ATP stimulates arachidonic acid mobilization and eicosanoid production in cultured astrocytes via P2Y-purinergic receptors. To assist in determining the mechanism of phospholipase A2 activation and the role of calcium in eicosanoid production, cultures were pretreated with pertussis toxin (PTx). ATP-evoked eicosanoid ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440070305

    authors: Bruner G,Murphy S

    更新日期:1993-03-01 00:00:00

  • Ca2+ influx into leech neuropile glial cells mediated by nicotinic acetylcholine receptors.

    abstract::The effect of cholinergic agonists and antagonists on the intracellular free Ca2+ concentration ([Ca2+]i) of leech neuropile glial cells was investigated by use of iontophoretically injected fura-2. In neuropile glial cells, cholinergic agonists induced a marked increase in [Ca2+]i that was inhibited by d-tubocurarine...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440150106

    authors: Hochstrate P,Schlue WR

    更新日期:1995-09-01 00:00:00

  • IL-27 inhibits OSM-mediated TNF-alpha and iNOS gene expression in microglia.

    abstract::Elevated levels of Oncostatin M (OSM), an interleukin-6 family cytokine, have been observed in multiple sclerosis (MS), HIV-associated neurocognitive disorder (HAND), and glioblastoma (GBM); however, its effects within the CNS are not well understood. OSM regulates gene expression primarily by activating the JAK/STAT,...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20989

    authors: Baker BJ,Park KW,Qin H,Ma X,Benveniste EN

    更新日期:2010-07-01 00:00:00

  • Stress-induced structural and functional modifications of astrocytes-Further implicating glia in the central response to stress.

    abstract::An organism's response to stress requires activation of multiple brain regions. This can have long-lasting effects on synaptic transmission and plasticity that likely provide adaptive benefits. Recent evidence implicates not only neurones, but also glial cells in the regulation of the central response to stress. Inten...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.23610

    authors: Murphy-Royal C,Gordon GR,Bains JS

    更新日期:2019-10-01 00:00:00

  • Hyperpolarization-activated ion currents in cultured rat cortical and spinal cord astrocytes.

    abstract::Hyperpolarization-activated currents were recorded from rat brain cortical and spinal cord astrocytes maintained in culture. Spinal cord astrocytes expressed primarily an inward rectifier potassium current characterized by time-dependent inactivation, a strong dependence on extracellular Na+ and insensitivity to intra...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-1136(199603)16:3<196::AID-GLIA2

    authors: Guatteo E,Stanness KA,Janigro D

    更新日期:1996-03-01 00:00:00

  • Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes.

    abstract::Microglia are classically considered to be immune cells in the brain, but have now been proven to be involved in neuronal activity as well. Here we stereologically analyzed the spatial arrangement of microglia in the mouse hippocampus. First, we estimated the numerical densities (NDs) of microglia identified by ionize...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20552

    authors: Jinno S,Fleischer F,Eckel S,Schmidt V,Kosaka T

    更新日期:2007-10-01 00:00:00

  • A novel role of microglial NADPH oxidase in mediating extra-synaptic function of norepinephrine in regulating brain immune homeostasis.

    abstract::Although the peripheral anti-inflammatory effect of norepinephrine (NE) is well documented, the mechanism by which this neurotransmitter functions as an anti-inflammatory/neuroprotective agent in the central nervous system (CNS) is unclear. This article aimed to determine the anti-inflammatory/neuroprotective effects ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22801

    authors: Jiang L,Chen SH,Chu CH,Wang SJ,Oyarzabal E,Wilson B,Sanders V,Xie K,Wang Q,Hong JS

    更新日期:2015-06-01 00:00:00

  • Role of the extracellular matrix in myelination of peripheral nerve.

    abstract::Assembly of the extracellular matrix (ECM) has been tightly linked to compact myelin formation in the peripheral nervous system. We recently demonstrated that myelination of dorsal root ganglion (DRG) axons by Schwann cells may occur in the absence of basal lamina. We have now determined whether laminin deposition occ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.1068

    authors: Podratz JL,Rodriguez E,Windebank AJ

    更新日期:2001-07-01 00:00:00

  • Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation.

    abstract::Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod-shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23523

    authors: Witcher KG,Bray CE,Dziabis JE,McKim DB,Benner BN,Rowe RK,Kokiko-Cochran ON,Popovich PG,Lifshitz J,Eiferman DS,Godbout JP

    更新日期:2018-12-01 00:00:00

  • Depression of parallel and climbing fiber transmission to Bergmann glia is input specific and correlates with increased precision of synaptic transmission.

    abstract::In the cerebellar cortex, Bergmann glia enclose the synapses of both parallel and climbing fiber inputs to the Purkinje neuron. The glia express Ca(2+)-permeable AMPA receptors, and the GLAST and GLT-1 classes of glutamate transporter, which are activated by glutamate released during synaptic transmission. We have pre...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20768

    authors: Balakrishnan S,Bellamy TC

    更新日期:2009-03-01 00:00:00

  • Glutamate transport by retinal Muller cells in glutamate/aspartate transporter-knockout mice.

    abstract::Glutamate transporters are involved in maintaining extracellular glutamate at a low level to ensure a high signal-to-noise ratio for glutamatergic neurotransmission and to protect neurons from excitotoxic damage. The mammalian retina is known to express the excitatory amino acid transporters, EAAT1-5; however, their s...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20097

    authors: Sarthy VP,Pignataro L,Pannicke T,Weick M,Reichenbach A,Harada T,Tanaka K,Marc R

    更新日期:2005-01-15 00:00:00

  • ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans.

    abstract::Inhibition of Rho-kinase (ROCK) with Y27632 stimulates sprouting by injured corticospinal tract and dorsal column tract axons, and accelerates functional recovery. However, regeneration of these axons across the glial scar was not observed. Here we examined the effects of Y27632 treatment on chondroitin sulfate proteo...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20466

    authors: Chan CC,Wong AK,Liu J,Steeves JD,Tetzlaff W

    更新日期:2007-03-01 00:00:00

  • In vitro evaluation of reactive astrocyte migration, a component of tissue remodeling in glaucomatous optic nerve head.

    abstract::In order to improve understanding of remodeling events in the glaucomatous optic nerve head, the migration of optic nerve head astrocytes was studied in vitro. Since elevated intraocular pressure is an important stress factor identified in glaucomatous eyes, optic nerve head astrocytes were incubated under physical st...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.1052

    authors: Tezel G,Hernandez MR,Wax MB

    更新日期:2001-05-01 00:00:00

  • Infusion of cytosine-arabinoside into the cerebrospinal fluid of the rat brain inhibits the microglial cell proliferation after hypoglossal nerve injury.

    abstract::The present study describes a method to inhibit selectively the microglial cell proliferation following peripheral nerve injury. Continuous infusion of cytosine-arabinoside (ARA-C) from an osmotic minipump to the fourth ventricle or cisterna magna completely blocks the proliferation of microglial cells that normally o...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440070404

    authors: Svensson M,Aldskogius H

    更新日期:1993-04-01 00:00:00

  • Microglia suppress the secondary progression of autoimmune encephalomyelitis.

    abstract::Secondary progressive multiple sclerosis (SPMS) is an autoimmune disease of the central nervous system (CNS) characterized by progressive motor dysfunction, sensory deficits, and visual problems. The pathological mechanism of SPMS remains poorly understood. In this study, we investigated the role of microglia, immune ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23640

    authors: Tanabe S,Saitoh S,Miyajima H,Itokazu T,Yamashita T

    更新日期:2019-09-01 00:00:00

  • Cell autonomous and noncell-autonomous role of NF-κB p50 in astrocyte-mediated fate specification of adult neural progenitor cells.

    abstract::In previous work, we demonstrated that NF-κB p50 acts as crucial regulator of adult hippocampal neural progenitor cells (ahNPC). Indeed, NF-κB p50 knockout (KO) mice are characterized by remarkably reduced hippocampal neurogenesis. As a follow up to that work, herein we show that when cultured in vitro, ahNPC from wil...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23085

    authors: Cvijetic S,Bortolotto V,Manfredi M,Ranzato E,Marengo E,Salem R,Canonico PL,Grilli M

    更新日期:2017-01-01 00:00:00

  • Artifact versus reality--how astrocytes contribute to synaptic events.

    abstract::The neuronal doctrine, developed a century ago regards neuronal networks as the sole substrate of higher brain function. Recent advances in glial physiology have promoted an alternative hypothesis, which places information processing in the brain into integrated neuronal-glial networks utilizing both binary (neuronal ...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.22288

    authors: Nedergaard M,Verkhratsky A

    更新日期:2012-07-01 00:00:00

  • Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrocytes.

    abstract::Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains, localized in the astrocyte plasma membrane. The regulation of AQP4 is believed to be important for the homeostasis of water in the brain, but the AQP4 regulatory mechanisms are not yet known. In this study, we investigated the effect of a p...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Nakahama K,Nagano M,Fujioka A,Shinoda K,Sasaki H

    更新日期:1999-02-01 00:00:00

  • The voltage-gated potassium channel Kv1.3 is required for microglial pro-inflammatory activation in vivo.

    abstract::Microglia show a rich repertoire of activation patterns regulated by a complex ensemble of surface ion channels, receptors, and transporters. We and others have investigated whether microglia vary their K+ channel expression as a means to achieve functional diversity. However, most of the prior studies were conducted ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23457

    authors: Di Lucente J,Nguyen HM,Wulff H,Jin LW,Maezawa I

    更新日期:2018-09-01 00:00:00

  • Effect of elevated K(+), hypotonic stress, and cortical spreading depression on astrocyte swelling in GFAP-deficient mice.

    abstract::Glial fibrillary acidic protein (GFAP) is the main component of intermediate filaments in astrocytes. To assess its function in astrocyte swelling, we compared astrocyte membrane properties and swelling in spinal cord slices of 8- to 10-day-old wild-type control (GFAP(+/+)) and GFAP-knockout (GFAP(-/-)) mice. Membrane...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.1084

    authors: Anderová M,Kubinová S,Mazel T,Chvátal A,Eliasson C,Pekny M,Syková E

    更新日期:2001-09-01 00:00:00

  • Cell death in the oligodendrocyte lineage: a molecular perspective of life/death decisions in development and disease.

    abstract::Cell death in the oligodendrocyte lineage occurs during development and in pathological conditions as the result of a balance between opposing molecular signals. This review focuses on the molecular mechanisms of activation of signal transduction pathways affecting life/death decisions in progenitor cells and in matur...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/(sici)1098-1136(20000115)29:2<124::aid-gli

    authors: Casaccia-Bonnefil P

    更新日期:2000-01-15 00:00:00

  • Pathophysiology of glia in perinatal white matter injury.

    abstract::Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbanc...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.22658

    authors: Back SA,Rosenberg PA

    更新日期:2014-11-01 00:00:00

  • Vimentin immunoreactive glial cells in the fish optic nerve: implications for regeneration.

    abstract::The poor regenerative ability of neurons of the central nervous system in mammals, as compared with their counterpart in fish or amphibians, is thought to stem from differences in their immediate nonneuronal environment and its response to axonal injury. We describe one aspect of the environmental response to axonal i...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440100104

    authors: Cohen I,Sivron T,Lavie V,Blaugrund E,Schwartz M

    更新日期:1994-01-01 00:00:00

  • Disruption of dopaminergic transmission remodels tripartite synapse morphology and astrocytic calcium activity within substantia nigra pars reticulata.

    abstract::The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia circuitry particularly sensitive to pathological dopamine depletion. Indeed, hyperactivity of SNr neurons is known to be responsible for some motor disorders characteristic of Parkinson's disease. The neuronal processing of basal...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22777

    authors: Bosson A,Boisseau S,Buisson A,Savasta M,Albrieux M

    更新日期:2015-04-01 00:00:00

  • Temporal dynamics of myelination in the zebrafish spinal cord.

    abstract::Knowledge of the precise timing of myelination is critical to the success of zebrafish-based in vivo screening strategies for potential remyelination therapies. This study provides a systematic review of the timing of myelination in the zebrafish spinal cord and a critique of techniques by which it may be accurately a...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20964

    authors: Buckley CE,Marguerie A,Alderton WK,Franklin RJ

    更新日期:2010-05-01 00:00:00

  • Denervated skeletal muscle stimulates migration of Schwann cells from the distal stump of transected peripheral nerve: an in vivo study.

    abstract::We have tested the stimulation of Schwann cell migration from the distal stump of a 1 week transected sciatic nerve of adult rats by denervated skeletal muscle. Migrating Schwann cells were distinguished by the presence of non-specific cholinesterase (nChE) activity and glial fibrillary acidic protein (GFAP) at a dist...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440120203

    authors: Dubový P,Svízenská I

    更新日期:1994-10-01 00:00:00

  • Myelin/oligodendrocyte glycoprotein (MOG) expression is associated with myelin deposition.

    abstract::We investigated the onset of expression of the myelin/oligodendrocyte glycoprotein (MOG) mRNA and protein in the developing mouse central nervous system. In situ hybridization on brain sections at different stages of embryonic and postnatal development showed that MOG transcripts were first detected at birth in the me...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-1136(199609)18:1<39::AID-GLIA4>

    authors: Solly SK,Thomas JL,Monge M,Demerens C,Lubetzki C,Gardinier MV,Matthieu JM,Zalc B

    更新日期:1996-09-01 00:00:00

  • Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes.

    abstract::The pro-apoptotic sphingolipid ceramide plays an emergent role in the etiology of Alzheimer's disease (AD), although its function for neurodegeneration is not known. We determined the concentration and composition of ceramide in hippocampal tissue from newborn presenilin 1 (PS1) knock-in (PS1M146V) mice, a mouse model...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20626

    authors: Wang G,Silva J,Dasgupta S,Bieberich E

    更新日期:2008-03-01 00:00:00

  • RNA-sequencing reveals oligodendrocyte and neuronal transcripts in microglia relevant to central nervous system disease.

    abstract::Expression profiling of distinct central nervous system (CNS) cell populations has been employed to facilitate disease classification and to provide insights into the molecular basis of brain pathology. One important cell type implicated in a wide variety of CNS disease states is the resident brain macrophage (microgl...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22754

    authors: Solga AC,Pong WW,Walker J,Wylie T,Magrini V,Apicelli AJ,Griffith M,Griffith OL,Kohsaka S,Wu GF,Brody DL,Mardis ER,Gutmann DH

    更新日期:2015-04-01 00:00:00

  • Undisturbed climbing fiber pruning in the cerebellar cortex of CX3 CR1-deficient mice.

    abstract::Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)-to-Purkinje cell (PC) synapse provides a suitable model to study pruning and pruning-relevant processes during early postnatal ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23842

    authors: Kaiser N,Pätz C,Brachtendorf S,Eilers J,Bechmann I

    更新日期:2020-11-01 00:00:00