Transcriptional Regulation of Glutamate Transporters

Martínez-Lozada, Zila; Guillem, Alain M.; Robinson, Michael B.

doi:10.1016/bs.apha.2016.01.004

Cited by 58 publications

(24 citation statements)

References 238 publications

(332 reference statements)

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“…Astrocytes are characterized by the expression of Slc1a3 ( Figure S1). Slc1a3 encodes SLC1A3 (GLAST, EAAT1), the main ionotropic glutamate transporter of the cerebellum [32]. Pathway analysis on genes enriched in astrocytes highlight the supportive functions of these cells in buffering ions and neurotransmitters (Table S2).…”

Section: Glial Cell Transcriptomesmentioning

confidence: 99%

Single Cell Transcriptome Analysis of Niemann–Pick Disease, Type C1 Cerebella

Cougnoux

Yerger

Fellmeth

et al. 2020

IJMS

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Niemann–Pick disease, type C1 (NPC1) is a lysosomal disease characterized by endolysosomal storage of unesterified cholesterol and decreased cellular cholesterol bioavailability. A cardinal symptom of NPC1 is cerebellar ataxia due to Purkinje neuron loss. To gain an understanding of the cerebellar neuropathology we obtained single cell transcriptome data from control (Npc1+/+) and both three-week-old presymptomatic and seven-week-old symptomatic mutant (Npc1−/−) mice. In seven-week-old Npc1−/− mice, differential expression data was obtained for neuronal, glial, vascular, and myeloid cells. As anticipated, we observed microglial activation and increased expression of innate immunity genes. We also observed increased expression of innate immunity genes by other cerebellar cell types, including Purkinje neurons. Whereas neuroinflammation mediated by microglia may have both neuroprotective and neurotoxic components, the contribution of increased expression of these genes by non-immune cells to NPC1 pathology is not known. It is possible that dysregulated expression of innate immunity genes by non-immune cells is neurotoxic. We did not anticipate a general lack of transcriptomic changes in cells other than microglia from presymptomatic three-week-old Npc1−/− mice. This observation suggests that microglia activation precedes neuronal dysfunction. The data presented in this paper will be useful for generating testable hypotheses related to disease progression and Purkinje neurons loss as well as providing insight into potential novel therapeutic interventions.

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Section: Glial Cell Transcriptomesmentioning

confidence: 99%

Single Cell Transcriptome Analysis of Niemann–Pick Disease, Type C1 Cerebella

Cougnoux

Yerger

Fellmeth

et al. 2020

IJMS

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“…The gene products are designated by the SLC1XX nomenclature. The human proteins use a homogeneous classification system of EAAT1-5, but 3 EAATs initially cloned from rat brain and rabbit intestine were given nonstandard names still used in animal model literature: Glutamate Aspartate Transporter 1 (GLAST) for EAAT1, Glutamate transporter 1 (GLT-1) for EAAT2, and Excitatory Amino Acid Carrier 1 (EAAC1) for EAAT3 ( Jensen et al, 2015 ; Martinez-Lozada et al, 2016 ). The EAATs take up glutamate against its concentration gradient driven by cotransport with 3 Na + and 1 H + alongside the export of 1 K + ( Figure 1 ) ( Grewer et al, 2008 ).…”

Section: Eaatsmentioning

confidence: 99%

Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Spencer

Kalivas

2017

International Journal of Neuropsychopharmacology

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Drug addiction has often been described as a “hijacking” of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past 20 years the addiction field has ascribed a critical role for glutamatergic transmission in the development of addiction. Chronic drug use produces enduring neuroadaptations in corticostriatal projections that are believed to contribute to a maladaptive deficit in inhibitory control over behavior. Much of this research focuses on the role played by ionotropic glutamate receptors directly involved in long-term potentiation and depression or metabotropic receptors indirectly modulating synaptic plasticity. Importantly, the balance between glutamate release and clearance tightly regulates the patterned activation of these glutamate receptors, emphasizing an important role for glutamate transporters in maintaining extracellular glutamate levels. Five excitatory amino acid transporters participate in active glutamate reuptake. Recent evidence suggests that these glutamate transporters can be modulated by chronic drug use at a variety of levels. In this review, we synopsize the evidence and mechanisms associated with drug-induced dysregulation of glutamate transport. We then summarize the preclinical and clinical data suggesting that glutamate transporters offer an effective target for the treatment of drug addiction. In particular, we focus on the role that altered glutamate transporters have in causing drug cues and contexts to develop an intrusive quality that guides maladaptive drug seeking behaviors.

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“…The process is known as “excitotoxicity” [9] which is associated with depression [10]. Astroglial glutamate transporter-1 (GLT-1) in rodents, also known as excitatory amino acid transporter-2 (EAAT-2) in human, functions to clear 90% glutamate spilled over the synaptic cleft [11, 12]. In physiology, glutamate transported into astrocytes is converted into glutamine by glutamate dehydrogenase (GS), which is released to extracellular and then absorbed by neurons.…”

Section: Introductionmentioning

confidence: 99%

Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat

Cheng

Abdoulaye

et al. 2019

Neural Plasticity

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Background and Objective. Chronic unexpected mild stress (CUMS) destroys synaptic plasticity of hippocampal regenerated neurons that may be involved in the occurrence of poststroke depression. Astrocytes uptake glutamate at the synapse and provide metabolic support for neighboring neurons. Currently, we aim to investigate whether CUMS inhibits synaptic formation of regenerated neurons through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. Method. We exposed the ischemic stroke rats to ceftriaxone, during the CUMS intervention period to determine the effects of GLT-1 on glutamate circulation by immunofluorescence and mass spectrometry and its influences to synaptic plasticity by western blot and transmission electron microscopy. Result. CUMS evidently reduced the level of astroglial GLT-1 in the hippocampus of the ischemic rats (p<0.05), resulting in smaller amount of glutamate being transported into astrocytes surrounding synapses (p<0.05), and then expression of synaptophysin was suppressed (p<0.05) in hippocampal dentate gyrus. The ultrastructures of synapses in dentate gyrus were adversely influenced including decreased proportion of smile synapses, shortened thickness of postsynaptic density, reduced number of vesicles, and widened average distance of the synaptic cleft (all p<0.05). Moreover, ceftriaxone can promote glutamate circulation and synaptic plasticity (all p<0.05) by raising astroglial GLT-1 (p<0.05) and then improve depressive behaviors of the CUMS-induced model rats (p<0.05). Conclusion. Our study shows that CUMS destroys synaptic plasticity of regenerated neurons in the hippocampus through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. This may indicate one potential pathogenesis of poststroke depression.

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Transcriptional Regulation of Glutamate Transporters

Cited by 58 publications

References 238 publications

Single Cell Transcriptome Analysis of Niemann–Pick Disease, Type C1 Cerebella

Single Cell Transcriptome Analysis of Niemann–Pick Disease, Type C1 Cerebella

Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse

Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat

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