Acute Treatment with Diphenyl Diselenide Inhibits Glutamate Uptake into Rat Hippocampal Slices and Modifies Glutamate Transporters, SNAP-25, and GFAP Immunocontent

In the physiological condition, glutamate acts as an excitatory neurotransmitter in the retina. However, excessive glutamate can be toxic to retinal neurons by overstimulation of the glutamate receptors. Glutamate excess is primarily attributed to perturbation in the homeostasis of the glutamate metabolism. Major pathway of glutamate metabolism consists of glutamate uptake by glutamate transporters followed by enzymatic conversion of glutamate to nontoxic glutamine by glutamine synthetase. Glutamate metabolism requires energy supply, and the energy loss inhibits the functions of both glutamate transporters and glutamine synthetase. In this review, we describe the present knowledge concerning the retinal glutamate metabolism under the physiological and pathological conditions.

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NMDA Receptor Activation Mediates Hydrogen Peroxide–Induced Pathophysiology in Rat Hippocampal Slices

Journal of Neurophysiology ◽

10.1152/jn.2002.87.6.2896 ◽

2002 ◽

Vol 87 (6) ◽

pp. 2896-2903 ◽

Cited By ~ 64

Author(s):

Marat V. Avshalumov ◽

Margaret E. Rice

Keyword(s):

Nmda Receptor ◽

Oxidative Damage ◽

Synaptic Transmission ◽

Glutamate Uptake ◽

Epileptiform Activity ◽

Hippocampal Slices ◽

Receptor Activation ◽

Nmda Receptor Antagonist ◽

Ros Generation ◽

Progressive Degeneration

Endogenous reactive oxygen species (ROS) can act as modulators of neuronal activity, including synaptic transmission. Inherent in this process, however, is the potential for oxidative damage if the balance between ROS production and regulation becomes disrupted. Here we report that inhibition of synaptic transmission in rat hippocampal slices by H2O2 can be followed by electrical hyperexcitability when transmission returns during H2O2 washout. As in previous studies, H2O2exposure (15 min) reversibly depressed the extracellular population spike (PS) evoked by Schaffer collateral stimulation. Recovery of PS amplitude, however, was typically accompanied by mild epileptiform activity. Inclusion of ascorbate (400 μM) during H2O2 washout prevented this pathophysiology. No protection was seen with isoascorbate, which is a poor substrate for the stereoselective ascorbate transporter and thus remains primarily extracellular. Epileptiform activity was also prevented by the N-methyl-d-aspartate (NMDA) receptor antagonist, dl-2-amino-5-phosphonopentanoic acid (AP5) during H2O2washout. Once hyperexcitability was induced, however, AP5 did not reverse it. When present during H2O2 exposure, AP5 did not alter PS depression by H2O2but did inhibit the recovery of PS amplitude seen during pulse-train stimulation (10 Hz, 5 s) in H2O2. Inhibition of glutamate uptake by l- trans-2,4-pyrrolidine dicarboxylate (PDC; 50 μM) during H2O2washout markedly enhanced epileptiform activity; coapplication of ascorbate with PDC prevented this. These data indicate that H2O2 exposure can cause activation of normally silent NMDA receptors, possibly via inhibition of redox-sensitive glutamate uptake. When synaptic transmission returns during H2O2 washout, enhanced NMDA receptor activity leads to ROS generation and consequent oxidative damage. These data reveal a pathological cycle that could contribute to progressive degeneration in neurological disorders that involve oxidative stress, including cerebral ischemia.

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Guanosine enhances glutamate uptake and oxidation, preventing oxidative stress in mouse hippocampal slices submitted to high glutamate levels

Brain Research ◽

10.1016/j.brainres.2020.147080 ◽

2020 ◽

Vol 1748 ◽

pp. 147080

Author(s):

Y. Nonose ◽

L.Z. Pieper ◽

J.S. da Silva ◽

A. Longoni ◽

R.V. Apel ◽

...

Keyword(s):

Oxidative Stress ◽

Glutamate Uptake ◽

Hippocampal Slices

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Guanosine is neuroprotective against oxygen/glucose deprivation in hippocampal slices via large conductance Ca2+-activated K+ channels, phosphatidilinositol-3 kinase/protein kinase B pathway activation and glutamate uptake

Neuroscience ◽

10.1016/j.neuroscience.2011.03.022 ◽

2011 ◽

Vol 183 ◽

pp. 212-220 ◽

Cited By ~ 50

Author(s):

T. Dal-Cim ◽

W.C. Martins ◽

A.R.S. Santos ◽

C.I. Tasca

Keyword(s):

Protein Kinase ◽

Protein Kinase B ◽

Glutamate Uptake ◽

Hippocampal Slices ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

K Channels ◽

Pathway Activation

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Treadmill Exercise Induces Hippocampal Astroglial Alterations in Rats

Neural Plasticity ◽

10.1155/2013/709732 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 24

Author(s):

Caren Bernardi ◽

Ana Carolina Tramontina ◽

Patrícia Nardin ◽

Regina Biasibetti ◽

Ana Paula Costa ◽

...

Keyword(s):

Physical Exercise ◽

Treadmill Exercise ◽

Brain Plasticity ◽

Glutamate Uptake ◽

Hippocampal Slices ◽

Brain Health ◽

Synaptic Remodeling ◽

Neuroprotective Strategy ◽

Uptake Activity ◽

Underlying Mechanisms

Physical exercise effects on brain health and cognitive performance have been described. Synaptic remodeling in hippocampus induced by physical exercise has been described in animal models, but the underlying mechanisms remain poorly understood. Changes in astrocytes, the glial cells involved in synaptic remodeling, need more characterization. We investigated the effect of moderate treadmill exercise (20 min/day) for 4 weeks on some parameters of astrocytic activity in rat hippocampal slices, namely, glial fibrillary acidic protein (GFAP), glutamate uptake and glutamine synthetase (GS) activities, glutathione content, and S100B protein content and secretion, as well as brain-derived neurotrophic factor (BDNF) levels and glucose uptake activity in this tissue. Results show that moderate treadmill exercise was able to induce a decrease in GFAP content (evaluated by ELISA and immunohistochemistry) and an increase in GS activity. These changes could be mediated by corticosterone, whose levels were elevated in serum. BDNF, another putative mediator, was not altered in hippocampal tissue. Moreover, treadmill exercise caused a decrease in NO content. Our data indicate specific changes in astrocyte markers induced by physical exercise, the importance of studying astrocytes for understanding brain plasticity, as well as reinforce the relevance of physical exercise as a neuroprotective strategy.

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Lesion-Induced Alterations in Astrocyte Glutamate Transporter Expression and Function in the Hippocampus

ISRN Neurology ◽

10.1155/2013/893605 ◽

2013 ◽

Vol 2013 ◽

pp. 1-16 ◽

Cited By ~ 11

Author(s):

Alexandra E. Schreiner ◽

Eric Berlinger ◽

Julia Langer ◽

Karl W. Kafitz ◽

Christine R. Rose

Keyword(s):

Cell Damage ◽

Glutamate Uptake ◽

Hippocampal Slices ◽

Glutamate Transporter ◽

Reactive Astrocytes ◽

Extracellular Glutamate ◽

Sodium Imaging ◽

Ca1 Area ◽

And Function ◽

Transporter Expression

Astrocytes express the sodium-dependent glutamate transporters GLAST and GLT-1, which are critical to maintain low extracellular glutamate concentrations. Here, we analyzed changes in their expression and function following a mechanical lesion in the CA1 area of organotypic hippocampal slices. 6-7 days after lesion, a glial scar had formed along the injury site, containing strongly activated astrocytes with increased GFAP and S100β immunoreactivity, enlarged somata, and reduced capability for uptake of SR101. Astrocytes in the scar’s periphery were swollen as well, but showed only moderate upregulation of GFAP and S100β and efficiently took up SR101. In the scar, clusters of GLT-1 and GLAST immunoreactivity colocalized with GFAP-positive fibers. Apart from these, GLT-1 immunoreactivity declined with increasing distance from the scar, whereas GLAST expression appeared largely uniform. Sodium imaging in reactive astrocytes indicated that glutamate uptake was strongly reduced in the scar but maintained in the periphery. Our results thus show that moderately reactive astrocytes in the lesion periphery maintain overall glutamate transporter expression and function. Strongly reactive astrocytes in the scar, however, display clusters of GLAST and GLT-1 immunoreactivity together with reduced glutamate transport activity. This reduction might contribute to increased extracellular glutamate concentrations and promote excitotoxic cell damage at the lesion site.

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