Expression of the glutamate transporter GLT1 in neural cells of the rat central nervous system: Non-radioactive in situ hybridization and comparative immunocytochemistry

Schmitt, Angelika; Asan, Esther; Püschel, Bernd; Jöns, Thomas; Kügler, P.

doi:10.1016/0306-4522(95)00477-7

Cited by 142 publications

(161 citation statements)

References 38 publications

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“…This would be in agreement with the observation that in adult tissue, EAAT2 is the predominant transporter in maintaining low extracellular glutamate (Rothstein et al, 1996) as well as having a high affinity for glutamate (Pines et al, 1992). In fact, mRNA levels (but not protein) for GLT-1, the animal homologue of EAAT2, have been detected also in mature hippocampal neurons (Schmitt et al, 1996). Additional studies in models of ischemic brain injury and in fetal ovine brain (Northington et a!., 1997) also suggested a neuronal expression of GLT-l.…”

Section: Neuronal Localization Of Eaat1 and Eaat2 During Developmentsupporting

confidence: 91%

“…On the basis of amino acid sequence homology, EAATI, EAAT2, and EAAT3 have 92-96% homology to the animal homologues (Arriza et al, 1994). EAATI (GLAST) and EAAT2 (GLT-l) have been localized to astroglia (Rothstein et al, 1994Chaudhry et al, 1995;Lehre et al, 1995;Schmitt et al, 1996), whereas EAAT3 (EAACI) was localized to neurons (Kanai and Hediger, 1992;Rothstein et al, 1994Velaz-Faircloth et al, 1996). Recently, two new glutamate transporters have been identified, EAAT4 and EAAT5, and they appear to have a unique property of gating chloride ions (Fairman et al, 1995;Arriza et al, 1997).…”

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confidence: 99%

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Distribution of Glutamate Transporter Subtypes During Human Brain Development

Bar-Peled

Ben-Hur

Biegon³

et al. 1997

Journal of Neurochemistry

135

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Abstract:In the mature brain, removal of glutamate from the synaptic cleft plays an important role in the maintenance of subtoxic levels of glutamate. This requirement is handled by a family of glutamate transporters, EAAT1, EAAT2, EAAT3, and EAAT4. Due to the involvement of glutamate also in neuronal development, it is believed that glutamate transport plays a role in developmental processes as well. Therefore, we have used immunohistochemical and immunoblot analysis to determine the distribution of the four glutamate transporters during human brain development using human pre-and postnatal brain tissue. Regional analysis showed that each transporter subtype has a unique distribution during development. EAAT2 was the most prominent glutamate transporter subtype and was highly enriched in cortex, basal ganglia, cerebellum, and thalamus in all ages examined. EAAT1 immunoreactivity was lower than that of EAAT2, with predominant localization in cortex, basal ganglia, hippocampus, and periventricular region. EAAT3 was located mainly in cortex, basal ganglia, and hippocampus, and EAAT4 was found only in cortex, hippocampus, and cerebellar cortex. The distinct regional distribution of various EAAT subtypes and also the transient expression of specific EAAT subtypes during development suggest multiple functional roles for glutamate transporters in the developing brain. Key Words: EAAT1 -EAAT2-EAAT3-EAAT4-lmmunohistochemistry-Fetal brain.

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Section: Neuronal Localization Of Eaat1 and Eaat2 During Developmentsupporting

confidence: 91%

mentioning

confidence: 99%

Distribution of Glutamate Transporter Subtypes During Human Brain Development

Bar-Peled

Ben-Hur

Biegon³

et al. 1997

Journal of Neurochemistry

135

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“…Alternatively, although GLT-1 is primarily astroglial in adult rat brain (Rothstein et al, 1994;Chaudhry et al, 1995;Lehre et al, 1995), in fetal rat brain, GLT-1 protein may also be expressed in neurons at levels in the cell body that are below the limits of immunological detection, but at levels sufficient for detection in growing axons. This latter possibility is supported by in situ studies showing GLT-1 mRNA in hippocampal neurons in adult (Torp et al, 1994;Lehre et al, 1996;Schmitt et al, 1996) and developing (Sutherland et al, 1996) brain and by immunocytochemical studies showing a transient expression of GLT-1 protein in neuronal cell bodies and axons in fetal ovine brain (Northington et al, 1997).…”

Section: Glt-1 Localization In White Matter During Late Embryogenesismentioning

confidence: 80%

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

Furuta¹,

1997

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Extracellular glutamate concentrations are regulated by glial and neuronal transporter proteins. Four glutamate transporter subtypes have been identified in rat brain; GLAST and GLT-1 are primarily astrocytic, whereas EAAC1 and EAAT4 are neuronal. Using immunoblotting and immunohistochemistry with subtype-specific antipeptide antibodies, we examined the protein expression and regional and cellular localization of each glutamate transporter subtype in embryonic and postnatal rat CNS. Each transporter had a specific pattern of expression. GLAST immunoreactivity was low prenatally but became enriched in cerebellar Bergmann glia early postnatally and then was also present in forebrain later postnatally. The posttranslational modification of GLAST was unique among the subtypes; glycosylated GLAST increased with maturation, whereas nonglycosylated protein decreased in abundance postnatally. GLT-1 was present in fetal brain and spinal cord, with expression progressively increasing to adult levels throughout the neuraxis by postnatal day 26. Transient expression of GLT-1 immunoreactivity along axonal pathways was observed prenatally, in contrast to the exclusive localization of GLT-1 to astrocytes in the adult CNS. EAAC1, localized to neurons, was enriched in forebrain, diencephalon, and hindbrain during prenatal and postnatal development. EAAC1 expression was greater in newborn brain compared with adult brain. EAAT4 had a region-specific distribution; EAAT4 was mainly in cerebellum, localized to Purkinje cells, with much lower levels in forebrain. EAAT4 levels increased in cerebellum with age. We conclude that during CNS development the expression of glutamate transporter subtypes is differentially regulated, regionally segregated, and coordinated.

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“…Similar motifs are also present in GLT1c, GLAST, EAAT4 and EAAT5, suggesting that interactions between glutamate transporters and PDZ proteins may be common. 57 Finally, given the fact that GLT1 isoforms do appear to be expressed in at least a subset of hippocampal neurons, [58][59][60][61] and the evidence for differential regulation, it seems important to address the possibility that one or more GLT1 isoforms could be regulated in an activity-dependent manner. Proving that activitydependent expression of GLT1 plays a functional role in long-term potentiation (LTP) would require the use of electrophysiological paradigms, demonstration that the protein is trafficked to the cell membrane, and evidence for functional glutamate uptake by GLT1 in response to stimulation.…”

Section: Localization Of Glt1mentioning

confidence: 99%

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

Lauriat

McInnes

2007

Mol Psychiatry

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The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate uptake in the brain and its dysregulation has been associated with multiple psychiatric and neurological disorders. However, investigation of this molecule has been complicated by its complex pattern of alternative splicing, including three coding isoforms and multiple 5 0 -and 3 0 -UTRs that may have a regulatory function. It is likely that these sequences permit modulation of EAAT2 expression with spatial, temporal and or activity-dependent specificity; however, few studies have attempted to delineate the function of these sequences. Additionally, there are problems with the use of antibodies to study protein localization, possibly due to posttranslational modification of critical amino acid residues. This review describes what is currently known about the regulation of EAAT2 mRNA and protein isoforms and concludes with a summary of studies showing dysregulation of EAAT2 in psychiatric and neurological disorders. EAAT2 has been either primarily or secondarily implicated in a multitude of neuropsychiatric diseases in addition to the normal physiology of learning and memory. Thus, this molecule represents an intriguing therapeutic target once we improve our understanding of how it is regulated under normal conditions.

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Expression of the glutamate transporter GLT1 in neural cells of the rat central nervous system: Non-radioactive in situ hybridization and comparative immunocytochemistry

Cited by 142 publications

References 38 publications

Distribution of Glutamate Transporter Subtypes During Human Brain Development

Distribution of Glutamate Transporter Subtypes During Human Brain Development

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

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