Distribution of Glutamate Transporter Subtypes During Human Brain Development

Bar-Peled, Osnat; Ben-Hur, H; Biegon, Anat; Groner, Yoram; Dewhurst, Stephen; Furuta, Akiko; Rothstein, Jeffrey D.

doi:10.1046/j.1471-4159.1997.69062571.x

Cited by 135 publications

(91 citation statements)

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“…Because EAAT3 and EAAT4 are expressed in neurons whereas EAAT1 and EAAT2 are expressed in astroglia, our results suggest an abnormality associated with neurons, but not astroglia, in the glutamate synapse (Bar-Peled et al 1997;Chaudhry et al 1995;Furuta et al 1997;Milton et al 1997;Rothstein et al 1994;Yamada et al 1996Yamada et al , 1997. Interestingly, we have previously reported abnormalities in EAAT1 and EAAT2, but not EAAT3 or EAAT4, mRNA expression in the thalamus, a finding consistent with the notion of localization of glutamatergic abnormalities within the synapse to specific cell types in given brain regions .…”

Section: Discussionsupporting

confidence: 91%

“…The best studied of the glutamate transporters, EAAT2 (called GLT-1 in the rat) accounts for ‫ف‬ 90% of forebrain glutamate reuptake in the rodent (Rothstein et al 1996;Tanaka et al 1997). The predominately glial expression of EAAT2 mRNA and protein, observed throughout the human brain, is highest in the forebrain (Bar-Peled et al 1997;Milton et al 1997). Similar to EAAT2, EAAT3 (called EAAC1 in the rat) protein expression in the human brain is detected in the frontal cortex and the hippocampus (Bar-Peled et al 1997).…”

mentioning

confidence: 99%

“…The transporters have specific patterns of cellular localization: EAAT1 and EAAT2 have been localized to astroglia, whereas EAAT3 and EAAT4 are localized to neurons (Bar-Peled et al 1997;Chaudhry et al 1995;Furuta et al 1997;Lehre et al 1995;Milton et al 1997;Rothstein et al 1994;Sims and Robinson 1999;Yamada et al 1996Yamada et al , 1997. The best studied of the glutamate transporters, EAAT2 (called GLT-1 in the rat) accounts for ‫ف‬ 90% of forebrain glutamate reuptake in the rodent (Rothstein et al 1996;Tanaka et al 1997).…”

mentioning

confidence: 99%

“…The predominately glial expression of EAAT2 mRNA and protein, observed throughout the human brain, is highest in the forebrain (Bar-Peled et al 1997;Milton et al 1997). Similar to EAAT2, EAAT3 (called EAAC1 in the rat) protein expression in the human brain is detected in the frontal cortex and the hippocampus (Bar-Peled et al 1997). EAAT3 is localized to both post-and presynaptic neuronal soma and is associated with ‫ف‬ 40% of rodent hippocampal glutamate transport (Rothstein et al 1994).…”

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confidence: 99%

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Striatal Excitatory Amino Acid Transporter Transcript Expression in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

McCullumsmith

Meador‐Woodruff

2002

Neuropsychopharmacology

179

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Because abnormalities of glutamatergic neurotransmission in psychiatric illness are likely not limited to glutamate receptor expression, we investigated expression of excitatory amino acid transporters (EAATs) in the striatum. The EAATs, normally expressed in both glia (EAAT1 and EAAT2) and neurons (EAAT3 and EAAT4), have previously been implicated in Huntington's disease, amyotrophic lateral sclerosis, and schizophrenia. In A growing literature suggests abnormal expression of ionotropic glutamate receptors in the brain in schizophrenia. The preponderance of these studies has detected complex and regionally specific alterations in ␣ -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptor expression, especially in cingulate cortex and medial temporal lobe structures (Akbarian et al. 1996;Aparicio-Legarza et al. 1998;Deakin et al. 1989;Eastwood et al. 1997aEastwood et al. , 1997bEastwood et al. , 1995Grimwood et al. 1999;Harrison et al. 1991;Healy et al. 1998;Humphries et al. 1996;Ibrahim et al. 2000;Kerwin et al. 1988Kerwin et al. , 1990Kornhuber et al. 1989; MeadorWoodruff and Healy 2000;Nishikawa et al. 1983;Noga et al. 1997;Ohnuma et al. 1998;Porter et al. 1997;Sokolov 1998). Recently, such studies have been extended to other brain regions associated with limbic circuitry felt to be disturbed in psychiatric illnesses, including the striatum. Increased NMDA receptor binding at both the glycine/D-serine coagonist site and the intrachannel MK801 site was detected in the putamen, and increased CNQX (an AMPA/kainate antagonist) binding was detected in the caudate in schizophrenia (Aparicio-Legarza et al. (Arriza et al. 1993;Utsunomiya-Tate et al. 1996). The transporters have specific patterns of cellular localization: EAAT1 and EAAT2 have been localized to astroglia, whereas EAAT3 and EAAT4 are localized to neurons (Bar-Peled et al. 1997;Chaudhry et al. 1995;Furuta et al. 1997;Lehre et al. 1995;Milton et al. 1997;Rothstein et al. 1994;Sims and Robinson 1999;Yamada et al. 1996Yamada et al. , 1997. The best studied of the glutamate transporters, EAAT2 (called GLT-1 in the rat) accounts for ‫ف‬ 90% of forebrain glutamate reuptake in the rodent (Rothstein et al. 1996;Tanaka et al. 1997). The predominately glial expression of EAAT2 mRNA and protein, observed throughout the human brain, is highest in the forebrain (Bar-Peled et al. 1997;Milton et al. 1997). Similar to EAAT2, EAAT3 (called EAAC1 in the rat) protein expression in the human brain is detected in the frontal cortex and the hippocampus (Bar-Peled et al. 1997). EAAT3 is localized to both post-and presynaptic neuronal soma and is associated with ‫ف‬ 40% of rodent hippocampal glutamate transport (Rothstein et al. 1994). In contrast, levels of EAAT1 (called GLAST in the rat) and EAAT4 protein expression in the rodent central nervous system (CNS) are highest in the cerebellum in the Bergmann glia and Purkinje cell types, respectively, whereas human studies of EAAT1 protein expression indicate high levels in the f...

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Striatal Excitatory Amino Acid Transporter Transcript Expression in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

McCullumsmith

Meador‐Woodruff

2002

Neuropsychopharmacology

179

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“…Abnormal epileptiform activity has been recorded from the EC region 91,92 and is reported to be the lead structure in the emergence of tonic discharges in mesial structures in a majority of patients with EC atrophy. 93,94 Some studies have reported neuronal loss and gliosis in superficial layers of the EC, 86 whereas others find no significant difference in neuronal densities in the EC of patients with and without hippocampal sclerosis. 95 However, gliosis was a common finding in the EC of sclerotic and nonsclerotic patients.…”

Section: Astrocytes May Contribute To the High Glutamate Levels At Thmentioning

confidence: 99%

Astrocytes and Epilepsy

2010

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Summary: Astrocytes form a significant constituent of seizure foci in the human brain. For a long time it was believed that astrocytes play a significant role in the causation of seizures. With the increase in our understanding of the unique biology of these cells, their precise role in seizure foci is receiving renewed attention. This article reviews the information now available on the role of astrocytes in the hippocampal seizure focus in patients with temporal lobe epilepsy with hippocampal sclerosis. Our intent is to try to integrate the available data. Astrocytes at seizure foci seem to not be a homogeneous population of cells, and in addition to typical glial fibrillary acidic protein, positive reactive astrocytes also include a population of neuron glia-2-like cells The astrocytes in sclerotic hippocampi differ from those in nonsclerotic hippocampi in their membrane physiology, having elevated Naϩ channels and reduced inwardly rectifying potassium ion channels, and some having the capacity to generate action potentials. They also have reduced glutamine synthetase and increased glutamate dehydrogenase activity. The molecular interface between the astrocyte and microvasculature is also changed. The astrocytes are also associated with increased expression of many molecules normally concerned with immune and inflammatory functions. A speculative mechanism postulates that neuron glia-2-like cells may be involved in creating a high glutamate environment, whereas the function of more typical reactive astrocytes contribute to maintain high extracellular Kϩ levels; both factors contributing to the hyperexcitability of subicular neurons to generate epileptiform activity. The functions of the astrocyte vascular interface may be more critical to the processes involved in epileptogenesis.

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Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons

et al. 1999

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Pigment epithelial-derived factor (PEDF) has been shown to be a survival factor for cerebellar granule neurons. Here we investigated the ability of PEDF to enhance the survival of hippocampal neurons in culture, and to protect these neurons against acute glutamate toxicity. Hippocampal neurons prepared from 1- to 3-day postnatal rat brain were cultured for either 7 or 14 days in vitro (DIV). At 14 DIV, neurons were only slightly protected (13% +/- 4%) against 50 microM glutamate toxicity when treated with 1 microg/ml of PEDF for 3 successive days before glutamate exposure as measured by lactate dehydrogenase (LDH) release. In comparison, basic fibroblast growth factor (bFGF) at 10 ng/ml for the same treatment period protected 58% +/- 8% of the neurons against glutamate. Using quantitative image analysis of digitized micrographs, we found that the average size of neurons in young, developing hippocampal cultures (7 DIV), was greatly decreased by treatment with 50 microM glutamate. Treatment for up to 5 successive days with 1 microg/ml of PEDF before glutamate addition dramatically increased the average hippocampal neuron soma size, compared to cells treated with glutamate alone. Thus, PEDF may promote the growth of hippocampal neurons, and, if added to developing hippocampal neurons, can also protect these cells from subsequent injury, such as the excitotoxicity of glutamate.

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Distribution of Glutamate Transporter Subtypes During Human Brain Development

Cited by 135 publications

References 25 publications

Striatal Excitatory Amino Acid Transporter Transcript Expression in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Striatal Excitatory Amino Acid Transporter Transcript Expression in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Astrocytes and Epilepsy

Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons

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