Myelin-associated glycoprotein activation triggers glutamate uptake by oligodendrocytes in vitro and contributes to ameliorate glutamate-mediated toxicity in vivo

2021 ◽  
pp. 166324
Author(s):  
Ana L. Vivinetto ◽  
Clara Castañares ◽  
Constanza Garcia-Keller ◽  
Ana Lis Moyano ◽  
Cristian Falcon ◽  
...  
Keyword(s):  
Glutamate Uptake ◽  
Myelin Associated Glycoprotein

Generation of Slow Network Oscillations in the Developing Rat Hippocampus After Blockade of Glutamate Uptake

2007 ◽  
Vol 98 (4) ◽  
pp. 2324-2336 ◽  
Author(s):  
Adriano Augusto Cattani ◽  
Valérie Delphine Bonfardin ◽  
Alfonso Represa ◽  
Yehezkel Ben-Ari ◽  
Laurent Aniksztejn
Keyword(s):  
Nmda Receptors ◽  
Glutamate Uptake ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Proper Function ◽  
Network Oscillations ◽  
Bath Application ◽  
Hippocampal Network

Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by dl-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. dl-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by γ-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-d-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.

scholarly journals Emergence of three myelin proteins in oligodendrocytes cultured without neurons.

1986 ◽  
Vol 102 (2) ◽  
pp. 384-392 ◽  
Author(s):  
M Dubois-Dalcq ◽  
T Behar ◽  
L Hudson ◽  
R A Lazzarini
Keyword(s):  
Optic Nerve ◽  
Proteolipid Protein ◽  
Defined Medium ◽  
Myelin Proteins ◽  
Specific Marker ◽  
The Central Nervous System ◽  
Double Label ◽  
Myelin Associated Glycoprotein

Oligodendrocytes, the myelin-forming cells of the central nervous system, were cultured from newborn rat brain and optic nerve to allow us to analyze whether two transmembranous myelin proteins, myelin-associated glycoprotein (MAG) and proteolipid protein (PLP), were expressed together with myelin basic protein (MBP) in defined medium with low serum and in the absence of neurons. Using double label immunofluorescence, we investigated when and where these three myelin proteins appeared in cells expressing galactocerebroside (GC), a specific marker for the oligodendrocyte membrane. We found that a proportion of oligodendrocytes derived from brain and optic nerve invariably express MBP, MAG, and PLP about a week after the emergence of GC, which occurs around birth. In brain-derived oligodendrocytes, MBP and MAG first emerge between the fifth and the seventh day after birth, followed by PLP 1 to 2 d later. All three proteins were confined to the cell body at that time, although an extensive network of GC positive processes had already developed. Each protein shows a specific cytoplasmic localization: diffuse for MBP, mostly perinuclear for MAG, and particulate for PLP. Interestingly, MAG, which may be involved in glial-axon interactions, is the first myelin protein detected in the processes at approximately 10 d after birth. MBP and PLP are only seen in these locations after 15 d. All GC-positive cells express the three myelin proteins by day 19. Simultaneously, numerous membrane and myelin whorls accumulate along the oligodendrocyte surface. The sequential emergence, cytoplasmic location, and peak of expression of these three myelin proteins in vitro follow a pattern similar to that described in vivo and, therefore, are independent of continuous neuronal influences. Such cultures provide a convenient system to study factors regulating expression of myelin proteins.

Modulation of voltage-dependent K+ currents (IK(V)) in retinal bipolar cells by ascorbate is mediated by dopamine D1 receptors

1999 ◽  
Vol 16 (5) ◽  
pp. 923-931 ◽  
Author(s):  
SHIH-FANG FAN ◽  
STEPHEN YAZULLA
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Uptake ◽  
Sch 23390 ◽  
D2 Receptor ◽  
Bipolar Cells ◽  
D1 Receptors ◽  
Voltage Dependent ◽  
Average Latency

Ascorbic acid (AA), a neuromodulator in the vertebrate CNS, is released from glutamatergic neurons in exchange with glutamate uptake and, in turn, modulates the release of both glutamate and dopamine. We have reported that voltage-gated K+ currents (IK(V)) in ON-mixed rod/cone bipolar cells (Mb) were suppressed 60% by 100–200 μM AA when added to an ascorbate-free solution. However, as the in vivo [AA]o in retina is about 200 μM, we studied the effects of changes in [AA]o on IK(V) when [AA]o was varied around a baseline concentration of 200 μM. Whole-cell currents were recorded with patch-clamp methods from goldfish Mb cells in retinal slices, bathed in a solution containing 200 μM AA. We found that (1) IK(V) was enhanced (180 ± 36%, n = 9) by increases of [AA]o less than 40 μM with an average latency of 8 min. (2) However, IK(V) was suppressed without an appreciable latent period by two conditions: increases more than 40 μM [AA]o and decreases by any amount greater than 10 μM. (3) Effects of Δ[AA]o on IK(V) were blocked by a D1 dopamine receptor antagonist, SCH 23390, but not by a D2 receptor antagonist, spiperone. Increased concentrations of a D1 agonist (SKF 38390) and dopamine had similar concentration-dependent effects on IK(V) as did AA, even in the presence of 200 μM ascorbate. Ascorbate has complicated concentration-dependent effects on IK(V) of Mb cells in vitro that were mediated by D1 dopamine receptors, suggesting that dopamine and ascorbate may be involved reciprocally in modulating IK(V), with consequences on the transmission of rod signals to the inner retina.

scholarly journals Neuroprotective Effects of Panax Notoginseng Saponins against Cerebral Ischemia via Improving Glutamate Metabolism Pathway: In Vivo and In Vitro

2020 ◽  
Author(s):  
Yuan Qiao ◽  
Qing Ma ◽  
Ya Li ◽  
Chunlan Fan ◽  
Minke Tang
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Atpase Activity ◽  
Glutamate Uptake ◽  
Glutamate Transporter ◽  
Panax Notoginseng ◽  
Glutamate Metabolism ◽  
Metabolism Pathway

Abstract Background: Ischemic stroke patients suffer from relatively limited treatment options. Studies have shown that glutamate is the most important excitatory neurotransmitter in the central nervous system. However, excessive glutamate in the extracellular cause cell apoptosis, and neurodegenerative processed after cerebral ischemia stroke. Glutamate metabolism pathway is necessary for glutamate clearance after ischemic stroke. Here we investigated the in vivo and in vitro effects of Panax Notoginseng Saponins (PNS) on glutamate metabolism pathway. Methods: we used mice impaired by middle cerebral artery occlusion (MCAO) and astrocytes exposed to oxygen-glucose deprivation/ reoxygenation (OGD/R) to test the potential mechanism of PNS. In vivo, we determined the cerebral infarction volume and measured brain water content. In vitro, we measured the astrocytes viability and evaluated the morphology of astrocyte. In addition, glutamate uptake, Na+-K+-ATPase activity, the expression levels of glutamate transporter GLT-1 and glutamine synthetase (GS) were determined in vivo and in vitro. Results: In vivo, we demonstrated that PNS could significantly decrease cerebral ischemia injury and improve neurological function in mice impaired by MCAO. In vitro, we found that PNS increased astrocytes viability, inhibited LDH leakage, and improved morphology of astrocytes under OGD/R. Additionally, we reported that both in vivo and in vitro, PNS enhanced the glutamate uptake and Na+-K+-ATPase activity, and up-regulated the expression levels of glutamate transporter GLT-1 and GS. Conclusion: this study suggested that PNS protects against cerebral ischemia induced brain damage. The possible mechanism is related with inhibiting glutamate accumulation by improving glutamate metabolism pathway.

Interaction between glutamate signalling and immune attack in damaging oligodendrocytes

2007 ◽  
Vol 3 (4) ◽  
pp. 281-285 ◽  
Author(s):  
Carlos Matute
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Uptake ◽  
Kainate Receptors ◽  
Glutamate Excitotoxicity ◽  
Excitatory Neurotransmitter ◽  
Glutamate Signaling ◽  
Immune Attack ◽  
Glutamate Homeostasis

AbstractGlutamate is the principal excitatory neurotransmitter in the CNS, but it is also a potent neurotoxin that can kill nerve cells. Glutamate damages oligodendrocytes, like neurons, by excitotoxicity which is caused by sustained activation of AMPA, kainate and NMDA receptors. Glutamate excitotoxicity depends entirely on Ca2+ overload of the cytoplasm and can be initiated by disruption of glutamate homeostasis. Thus, inhibition of glutamate uptake in isolated oligodendrocytes in vitro and in the optic nerve in vivo, is sufficient to trigger cell death which is prevented by glutamate receptor antagonists. In turn, activated, but not resting microglia, can compromise glutamate homeostasis and induce oligodendrocyte excitotoxicity, which is attenuated either by AMPA/kainate antagonists or by the blockade of the system xc_ antiporter present in microglia. By contrast, non-lethal, brief, activation of glutamate receptors in oligodendrocytes rapidly sensitizes these cells to complement attack. Intriguingly, these effects are exclusively mediated by kainate receptors which induce Ca2+ overload of the cytosol and the generation of reactive oxygen species. In conjunction, these observations reveal novel mechanisms by which neuroinflammation alters glutamate homeostasis and triggers oligodendrocyte death. Conversely, they also show how glutamate signaling in oligodendrocytes might induce immune attack. In both instances direct activation of glutamate receptors present in oligodendrocytes plays a pivotal role in either initiating or executing death signals, which might be relevant to the pathogenesis of white matter disorders.

scholarly journals Myelin-associated glycoprotein, a cell adhesion molecule of oligodendrocytes, is phosphorylated in brain.

1988 ◽  
Vol 8 (6) ◽  
pp. 2655-2658 ◽  
Author(s):  
A M Edwards ◽  
M Arquint ◽  
P E Braun ◽  
J C Roder ◽  
R J Dunn ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Cell Adhesion Molecule ◽  
Protein Tyrosine Kinases ◽  
Developmentally Regulated ◽  
Myelin Membrane ◽  
Tyrosine Residues ◽  
A Cell ◽  
Myelin Associated Glycoprotein

Myelin-associated glycoprotein (MAG) has been implicated in the mediation of interactions between oligodendrocytes and neurons during the development of the myelin sheath. Here we show that MAG is phosphorylated in intact myelinating mouse brain primarily at serine residues and to a lesser extent at threonine and tyrosine residues. In vivo, only the larger of the two developmentally regulated MAG isoforms is phosphorylated. MAG can be phosphorylated at tyrosine by the v-fps and v-src protein-tyrosine kinases in vitro and by a kinase endogenous to myelin membrane preparations. MAG phosphorylated in myelin membranes in vitro also contains phosphoserine and phosphothreonine. These observations suggest that phosphorylation of MAG is physiologically significant in regulating oligodendrocyte-neuron interactions.

scholarly journals Nordihydroguaiaretic acid increases glutamate uptake in vitro and in vivo: Therapeutic implications for amyotrophic lateral sclerosis

2008 ◽  
Vol 213 (1) ◽  
pp. 229-237 ◽  
Author(s):  
William Boston-Howes ◽  
Eric O. Williams ◽  
Alexey Bogush ◽  
Maura Scolere ◽  
Piera Pasinelli ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Glutamate Uptake ◽  
Nordihydroguaiaretic Acid ◽  
Therapeutic Implications ◽  
Lateral Sclerosis

scholarly journals Anomalous glutamate/alkali cation symport in larval Manduca sexta midgut.

1994 ◽  
Vol 194 (1) ◽  
pp. 181-194
Author(s):  
T Xie ◽  
R Parthasarathy ◽  
M G Wolfersberger ◽  
W R Harvey
Keyword(s):  
Manduca Sexta ◽  
Brush Border Membrane ◽  
Glutamate Uptake ◽  
Membrane Vesicles ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Cation Uptake ◽  
Initial Uptake

Rapid filtration assays were used to characterize glutamate/cation uptake in brush-border membrane vesicles from the larval midgut of the lepidopteran Manduca sexta. At pH 10.5, which is close to the physiological pH in the midgut of M. sexta, an inwardly directed K+ gradient stimulated glutamate uptake, suggesting that glutamate was symported. Gradients of Na+ or Li+ were less effective. Neither Rb+ nor Cs+ stimulated glutamate uptake. Anion-specificity was less pronounced: the accumulation maximum was only slightly higher with thiocyanate (SCN-) than with Cl-, although initial uptake was noticeably faster with thiocyanate. A distinct set of amino acids that would cis-inhibit or trans-elicit glutamate uptake was not found. Even L-glutamate itself did not elicit accumulations of labeled glutamate. Taken together, these results suggest that a glutamate-specific symporter may not be present. Moreover, because glutamate symport was found to be electroneutral in vitro whereas amino acid uptake is electrophoretic in vivo, we infer that symport with K+ may not be an important mechanism of glutamate translocation by M. sexta midgut.

scholarly journals Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination.

1993 ◽  
Vol 123 (5) ◽  
pp. 1223-1236 ◽  
Author(s):  
S Einheber ◽  
T A Milner ◽  
F Giancotti ◽  
J L Salzer
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cell Contact ◽  
Myelin Associated Glycoprotein ◽  
Dorsal Root Ganglia Neurons ◽  
Outer Plasma Membrane

Ensheathment and myelination of axons by Schwann cells in the peripheral nervous system requires contact with a basal lamina. The molecular mechanism(s) by which the basal lamina promotes myelination is not known but is likely to reflect the activity of integrins expressed by Schwann cells. To initiate studies on the role of integrins during myelination, we characterized the expression of two integrin subunits, beta 1 and beta 4, in an in vitro myelination system and compared their expression to that of the glial adhesion molecule, the myelin-associated glycoprotein (MAG). In the absence of neurons, Schwann cells express significant levels of beta 1 but virtually no beta 4 or MAG. When Schwann cells are cocultured with dorsal root ganglia neurons under conditions promoting myelination, expression of beta 4 and MAG increased dramatically in myelinating cells, whereas beta 1 levels remained essentially unchanged. (In general agreement with these findings, during peripheral nerve development in vivo, beta 4 levels also increase during the period of myelination in sharp contrast to beta 1 levels which show a striking decrease.) In cocultures of neurons and Schwann cells, beta 4 and MAG appear to colocalize in nascent myelin sheaths but have distinct distributions in mature sheaths, with beta 4 concentrated in the outer plasma membrane of the Schwann cell and MAG localized to the inner (periaxonal) membrane. Surprisingly, beta 4 is also present at high levels with MAG in Schmidt-Lanterman incisures. Immunoprecipitation studies demonstrated that primary Schwann cells express beta 1 in association with the alpha 1 and alpha 6 subunits, while myelinating Schwann cells express alpha 6 beta 4 and possibly alpha 1 beta 1. beta 4 is also downregulated during Wallerian degeneration in vitro, indicating that its expression requires continuous Schwann cell contact with the axon. These results indicate that axonal contact induces the expression of beta 4 during Schwann cell myelination and suggest that alpha 6 beta 4 is an important mediator of the interactions of myelinating Schwann cells with the basal lamina.

Myelin-associated glycoprotein, a cell adhesion molecule of oligodendrocytes, is phosphorylated in brain

1988 ◽  
Vol 8 (6) ◽  
pp. 2655-2658
Author(s):  
A M Edwards ◽  
M Arquint ◽  
P E Braun ◽  
J C Roder ◽  
R J Dunn ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Cell Adhesion Molecule ◽  
Protein Tyrosine Kinases ◽  
Developmentally Regulated ◽  
Myelin Membrane ◽  
Tyrosine Residues ◽  
A Cell ◽  
Myelin Associated Glycoprotein

Myelin-associated glycoprotein (MAG) has been implicated in the mediation of interactions between oligodendrocytes and neurons during the development of the myelin sheath. Here we show that MAG is phosphorylated in intact myelinating mouse brain primarily at serine residues and to a lesser extent at threonine and tyrosine residues. In vivo, only the larger of the two developmentally regulated MAG isoforms is phosphorylated. MAG can be phosphorylated at tyrosine by the v-fps and v-src protein-tyrosine kinases in vitro and by a kinase endogenous to myelin membrane preparations. MAG phosphorylated in myelin membranes in vitro also contains phosphoserine and phosphothreonine. These observations suggest that phosphorylation of MAG is physiologically significant in regulating oligodendrocyte-neuron interactions.

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