Downregulation of glutamate transporters is associated with elevation in extracellular glutamate concentration following rat microsphere embolism

2008 ◽  
Vol 430 (3) ◽  
pp. 275-280 ◽  
Author(s):  
Feng Han ◽  
Norifumi Shioda ◽  
Shigeki Moriguchi ◽  
Zheng-Hong Qin ◽  
Kohji Fukunaga
Keyword(s):  
Glutamate Transporters ◽  
Extracellular Glutamate ◽  
Glutamate Concentration ◽  
Microsphere Embolism

The role of glutamate transporters in glutamate homeostasis in the brain.

1997 ◽  
Vol 200 (2) ◽  
pp. 401-409 ◽  
Author(s):  
M Takahashi ◽  
B Billups ◽  
D Rossi ◽  
M Sarantis ◽  
M Hamann ◽  
...  
Keyword(s):  
Extracellular Space ◽  
Glutamate Release ◽  
Glutamate Transporters ◽  
Extracellular Glutamate ◽  
Physical Handicap ◽  
Glutamate Concentration ◽  
Anion Conductance ◽  
Glutamatergic Synaptic Transmission ◽  
The Brain

Glutamate transporters in neurones and glia, four of which have been cloned from mammals, play a crucial role in controlling the extracellular glutamate concentration in the brain. In normal conditions, they remove glutamate from the extracellular space and thereby help to terminate glutamatergic synaptic transmission and to prevent the extracellular glutamate concentration from rising to neurotoxic values. Glutamate transport on these carriers is thought to be driven by the cotransport of Na+, the counter-transport of K+, and either the cotransport of H+ or the counter-transport of OH-. Activating the transporters also activates an anion conductance in their structure, the anion flux through which is not coupled to glutamate movement and varies widely for the different transporters. During hypoxia or ischaemia, glutamate transporters can run backwards, releasing glutamate into the extracellular space, triggering the death of neurones and thus causing mental and physical handicap. The rate of glutamate release by this process is slowed by the acid pH occurring in hypoxia/ischaemia, which may help protect the brain during transient, but not sustained, ischaemia.

scholarly journals Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse

2013 ◽  
Vol 109 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Jessica L. Hauser ◽  
Eleanore B. Edson ◽  
Bryan M. Hooks ◽  
Chinfei Chen
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Time Course ◽  
Ganglion Cells ◽  
Glutamate Transporters ◽  
Decay Kinetics ◽  
Metabotropic Glutamate ◽  
Glutamate Concentration ◽  
Group Ii ◽  
Retinogeniculate Synapse

Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (dl- threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.

scholarly journals Effects of Cocaine Exposure on Astrocytic Glutamate Transporters and Relapse-Like Ethanol-Drinking Behavior in Male Alcohol-Preferring Rats

2020 ◽  
Vol 55 (3) ◽  
pp. 254-263 ◽  
Author(s):  
Alaa M Hammad ◽  
Youssef Sari
Keyword(s):  
Drugs Of Abuse ◽  
Drinking Behavior ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Brain Regions ◽  
Ethanol Intake ◽  
Free Access ◽  
Cocaine Exposure ◽  
Extracellular Glutamate ◽  
Lactam Antibiotic

Abstract Aim Glutamate has been considered as neurotransmitter that is critical in triggering relapse to drugs of abuse, including ethanol and cocaine. Extracellular glutamate concentrations are tightly regulated by several mechanisms, including reuptake through glutamate transporters. Glutamate transporter type 1 (GLT-1) is responsible for clearing the majority of extracellular glutamate. The astrocytic cystine/glutamate antiporter (xCT) regulates also glutamate homeostasis. In this study, we investigated the effects of cocaine exposure and ampicillin/sulbactam (AMP/SUL), a β-lactam antibiotic known to upregulate GLT-1 and xCT, on relapse-like ethanol intake and the expression of astrocytic glutamate transporters in mesocorticolimbic brain regions. Methods Male alcohol-preferring (P) rats had free access to ethanol for 5 weeks. On Week 6, rats were exposed to either cocaine (20 mg/kg, i.p.) or saline for 12 consecutive days. Ethanol bottles were then removed for 7 days; during the last 5 days, either AMP/SUL (100 or 200 mg/kg, i.p.) or saline was administered to the P rats. Ethanol bottles were reintroduced, and ethanol intake was measured for 4 days. Results Cocaine exposure induced an alcohol deprivation effect (ADE), which was associated in part by a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc) core. AMP/SUL (100 mg/kg, i.p.) attenuated the ADE, while AMP/SUL (200 mg/kg, i.p.) reduced ethanol intake during 4 days of ethanol re-exposure and upregulated GLT-1 and xCT expression in the NAc core, NAc shell and dorsomedial prefrontal cortex (dmPFC). Conclusion This study suggests that these astrocytic glutamate transporters might be considered as potential targets for the treatment of polysubstance abuse.

Benzophenone-3 Passes Through the Blood-Brain Barrier, Increases the Level of Extracellular Glutamate, and Induces Apoptotic Processes in the Hippocampus and Frontal Cortex of Rats

2019 ◽  
Vol 171 (2) ◽  
pp. 485-500 ◽  
Author(s):  
Bartosz Pomierny ◽  
Weronika Krzyżanowska ◽  
Żaneta Broniowska ◽  
Beata Strach ◽  
Beata Bystrowska ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Blood Brain Barrier ◽  
Brain Structures ◽  
Glutamate Transporters ◽  
Brain Barrier ◽  
Short Term ◽  
Extracellular Glutamate ◽  
Blood Brain ◽  
The Impact ◽  
The Brain

Abstract Benzophenone-3 is the most commonly used UV filter. It is well absorbed through the skin and gastrointestinal tract. Its best-known side effect is the impact on the function of sex hormones. Little is known about the influence of BP-3 on the brain. The aim of this study was to show whether BP-3 crosses the blood-brain barrier (BBB), to determine whether it induces nerve cell damage in susceptible brain structures, and to identify the mechanism of its action in the central nervous system. BP-3 was administered dermally during the prenatal period and adulthood to rats. BP-3 effect on short-term and spatial memory was determined by novel object and novel location recognition tests. BP-3 concentrations were assayed in the brain and peripheral tissues. In brain structures, selected markers of brain damage were measured. The study showed that BP-3 is absorbed through the rat skin, passes through the BBB. BP-3 raised oxidative stress and induced apoptosis in the brain. BP-3 increased the concentration of extracellular glutamate in examined brain structures and changed the expression of glutamate transporters. BP-3 had no effect on short-term memory but impaired spatial memory. The present study showed that dermal BP-3 exposure may cause damage to neurons what might be associated with the increase in the level of extracellular glutamate, most likely evoked by changes in the expression of GLT-1 and xCT glutamate transporters. Thus, exposure to BP-3 may be one of the causes that increase the risk of developing neurodegenerative diseases.

A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat

1996 ◽  
Vol 85 (1) ◽  
pp. 104-111 ◽  
Author(s):  
Eiji Tsuchida ◽  
John F. Harms ◽  
John J. Woodward ◽  
Ross Bullock
Keyword(s):  
Sodium Channel ◽  
Subdural Hematoma ◽  
Neuronal Damage ◽  
Glutamate Release ◽  
Acute Subdural Hematoma ◽  
Extracellular Glutamate ◽  
Ischemic Brain ◽  
Content Type ◽  
Glutamate Concentration ◽  
Fine Print

✓ Acute subdural hematoma kills or disables more severely head injured patients than any other complication of cranial trauma. The main pathological factor involved is ischemic neuronal damage, which is caused by raised intracranial pressure and local effect. The authors have evaluated the hypothesis that a novel use-dependent sodium channel antagonist, 619C89, could reduce ischemic brain damage in the rat subdural hematoma model. Because previous studies have shown that focal neuronal damage may be mediated by “excitotoxic” mechanisms, and because excitatory amino acid levels have been shown to be markedly elevated after brain trauma in humans, the authors have measured levels of glutamate, aspartate, and threonine within the cortex underneath the hematoma, using in vivo microdialysis before and after induction of hematoma, in both vehicle- and drug-treated rats. Postinjury treatment with 619C89 (30 mg/kg) significantly reduced the volume of hemispheric ischemic damage produced by subdural hematoma, from 99.77 ± 7.51 mm3 in vehicle-treated control rats to 46.07 ± 11.06 mm3 (p = 0.0007) in drug-treated animals. In the vehicle-treated animals, induction of subdural hematoma led to a fourfold increase in glutamate in the first 30 minutes after subdural hematoma occurred. The mean extracellular glutamate concentration in these animals remained 2- to 2.6-fold increased over the following 2.5 hours. In the 619C89-treated animals, the release of glutamate from the cortex underneath the hematoma was significantly attenuated. In these rats, induction of subdural hematoma led to a 2.7-fold increase in the first 30-minute sample, but extracellular glutamate concentration returned to near-basal levels thereafter, compared with vehicle-treated animals (p < 0.05). These results show that 619C89 is highly neuroprotective in this model and that its effects may, in part, be mediated by the inhibiton of glutamate release from the ischemic cortex underneath the hematoma.

scholarly journals Effect of nicergoline on the removal of extracellular glutamate via the glutamate transporters

1998 ◽  
Vol 76 ◽  
pp. 85
Author(s):  
Atsushi Nishida ◽  
Tsutpmu Kobayashi ◽  
Yykitsuka Kudo ◽  
Yuzo Matsuoka
Keyword(s):  
Glutamate Transporters ◽  
Extracellular Glutamate

Long-Term Potentiation in the Dentate Gyrus Is Not Linked to Increased Extracellular Glutamate Concentration

1999 ◽  
Vol 81 (4) ◽  
pp. 1741-1748 ◽  
Author(s):  
T. M. Jay ◽  
E. Zilkha ◽  
T. P. Obrenovitch
Keyword(s):  
Dentate Gyrus ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Mammalian Brain ◽  
Excitatory Postsynaptic Potential ◽  
Extracellular Glutamate ◽  
Glutamate Concentration ◽  
Term Potentiation

Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration. Long-term potentiation (LTP) of excitatory transmission is a likely candidate for the encoding and storage of information in the mammalian brain. There is a general agreement that LTP involves an increase in synaptic strength, but the mechanisms underlying this persistent change are unclear and controversial. Synaptic efficacy may be enhanced because more transmitter glutamate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular glutamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection of any putative change in extracellular glutamate associated with LTP, our experimental strategy included the following features. 1) Two separate series of experiments were carried out with animals under pentobarbital or urethan anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsynaptic potential evoked by activation of the perforant path were recorded precisely at the same site. Tetanic stimulation of the perforant path increased persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results do not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data supporting the notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft conflict with the hypothesis that LTP could also involve a broad synaptic spillover of glutamate.

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