Glutamate transport in cultures from developing avian cerebellum: Presence of GLT-1 immunoreactivity in Purkinje neurons

Meaney, J.; Balcar, Vladimír J.; Rothstein, Jeffrey D.; Jeffrey, Peter L.

doi:10.1002/(sici)1097-4547(19981201)54:5<595::aid-jnr4>3.0.co;2-q

Cited by 24 publications

(7 citation statements)

References 44 publications

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“…Brooks-Kayal et al, 1998;Mennerick et al, 1998;Meaney et al, 1998;Wang et al, 1998a;Plachez et al, 2000). Further, EAAT2 had also been reported in neurons in the normal and mature mammalian retina (Rauen, 2000;Harada et al, 1998), transiently in growing axons of the mouse spinal cord before establishing astrocytic expression , and in brain neurons after hypoxiaischemia .…”

Section: Eaat2mentioning

confidence: 95%

Neuronal vs glial glutamate uptake: Resolving the conundrum

Danbolt

Furness

Zhou

2016

Neurochemistry International

180

152

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Neither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that both astrocytes and neurons express glutamate transporters. However, the relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) a hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox. ABBREVIATIONSCre, Cyclization recombinase (Le and Sauer, 2000); EAAC1, glutamate transporter (EAAT3; slc1a1; Kanai and Hediger, 1992; Bjørås et al., 1996); EAAT, excitatory amino acid transporter (synonym to glutamate transporter); GABA, γ-aminobutyric acid; GLAST, rat glutamate transporter (EAAT1; slc1a3; Storck et al., 1992;Tanaka, 1993a); GLT-1, rat glutamate transporter (EAAT2; slc1a2; Pines et al., 1992); GLUL, glutamine synthetase; TBOA, DL-threo-β-benzyloxyaspartate AbstractNeither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that astrocytes and neurons express glutamate transporters. The relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) an hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox.

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Section: Eaat2mentioning

confidence: 95%

Neuronal vs glial glutamate uptake: Resolving the conundrum

Danbolt

Furness

Zhou

2016

Neurochemistry International

180

152

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“…16,17) found not only in astrocytes but also in neurons, particularly in hippocampal cultures [78][79][80][81][82][83] and in Purkinje cells originating from an avian cerebellum. 84) In some cases the immunocytochemical detection has been supported by data on uptake 84,85) so that the evidence of a functional, GLT-mediated (or GLAST-mediated 83,85) ) glutamate transport located in such neurons is very convincing. The expression of GluT in developing neurons in situ also seems to take place but it appears to be a transient phenomenon, 86) perhaps typical of the regions of developing brain undergoing rapid cell proliferation and/or synaptogenesis.…”

Section: Location Of Glutamate Transporters In the Cnsmentioning

confidence: 97%

Molecular Pharmacology of the Na+-Dependent Transport of Acidic Amino Acids in the Mammalian Central Nervous System.

Balcar

2002

Biological & Pharmaceutical Bulletin

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The crucial discovery of the excitatory properties of acidic amino acids [2][3][4][5] lead only gradually and with considerable delay, to the formulation of the hypothesis of the synaptic role of L-glutamate in the mammalian central nervous system (CNS) 6-9) (for reviews of early history of amino acid research, see [10][11][12][13] ). It may never be possible to identify any single experimental study after which L-glutamate became unequivocally accepted as the most important excitatory synaptic transmitter in the brain and spinal cord, but, it is certain that the discovery of the "high affinity uptake" accumulating L-glutamate into "synaptosomes" 14,15) (for reviews see 13,16,17) ) was an important step in the development of the concept of the glutamatergic neurotransmission in the CNS. As a putative mechanism for the necessary removal and inactivation of extracellular L-glutamate it provided a target for pharmacological studies and helped to establish a neurochemical link between L-glutamate and the mechanisms of synaptic transmission. 13,18,19) Most of the latter experiments were carried out in vitro using tissue "mini-slices" prepared from the rat cerebral cortex or cat spinal cord (for details of the methodology see 20,21) ). Rather than disrupting the nervous tissue by homogenization, the technique was using what might be called "neurochemical dissection". In more specific terms, it examined a large number of compounds, mostly glutamate and aspartate analogues but also a range of drugs, for possible effects on L-glutamate transport (GluT). Such approach had a potential to yield valuable information on the molecular properties of the substrate-recognition site on GluT,19) but, also, by testing neuroactive compounds with known sites of actions in brain, it helped to formulate hypotheses defining the most probable functions of the GluT in the mechanisms of the excitatory synaptic transmission.The pharmacology and biochemistry of GluT was later extensively investigated in cultured glial cells [22][23][24] (for a review see 25) ) but it was the data obtained in anaesthetised animals, using compounds (D-and L-threo-3-hydroxyaspartate, DL-t3OHA) identified earlier as powerful specific inhibitors of [ 3 H]L-glutamate uptake in brain slices, 26) that provided the first convincing evidence that GluT could influence the excitatory actions of L-glutamate in vivo, at least in the cat spinal cord.27) Furthermore, if the inhibition of GluT in vivo caused an increase in the extracellular concentrations of L-glutamate then, given the neurotoxic nature of excessive glutamatergic excitation, 28,29) similar inhibition of GluT applied to functioning synapses should, under suitable experimental conditions, result in the appearance of neurodegeneration. Such experiment was indeed performed and it was shown that an injection of DL-t3OHA into the rat striatum could cause the death of brain cells in vivo. 30) HETEROGENEITY OF GLUTAMATE TRANSPORTDuring the 1980's and early 1990's, it became apparent that, in order to account for th...

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“…In developing nervous tissue, particularly in developing cultured brain cells, EAAT2/GLT1 is present, at least transiently, in neurons [19,20] where L-Glu may be involved in the process of differentiation [21]. Moreover, in the adult brain there is evidence of significant glutamate transport in axonal nerve endings, possibly mediated by a form of EAAT2/GLT1 [22][23][24] that is expressed by neurons.…”

Section: Location Of Eaats and Their Possible Roles In Brain Functionsmentioning

confidence: 99%

GLAST But Not Least—Distribution, Function, Genetics and Epigenetics of l-Glutamate Transport in Brain—Focus on GLAST/EAAT1

et al. 2015

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Synaptically released L-glutamate, the most important excitatory neurotransmitter in the CNS, is removed from extracellular space by fast and efficient transport mediated by several transporters; the most abundant ones are EAAT1/GLAST and EAAT2/GLT1. The review first summarizes their location, functions and basic characteristics. We then look at genetics and epigenetics of EAAT1/GLAST and EAAT2/GLT1 and perform in silico analyses of their promoter regions. There is one CpG island in SLC1A2 (EAAT2/GLT1) gene and none in SLC1A3 (EAAT1/GLAST) suggesting that DNA methylation is not the most important epigenetic mechanism regulating EAAT1/GLAST levels in brain. There are targets for specific miRNA in SLC1A2 (EAAT2/GLT1) gene. We also note that while defects in EAAT2/GLT1 have been associated with various pathological states including chronic neurodegenerative diseases, very little is known on possible contributions of defective or dysfunctional EAAT1/GLAST to any specific brain disease. Finally, we review evidence of EAAT1/GLAST involvement in mechanisms of brain response to alcoholism and present some preliminary data showing that ethanol, at concentrations which may be reached following heavy drinking, can have an effect on the distribution of EAAT1/GLAST in cultured astrocytes; the effect is blocked by baclofen, a GABA-B receptor agonist and a drug potentially useful in the treatment of alcoholism. We argue that more research effort should be focused on EAAT1/GLAST, particularly in relation to alcoholism and drug addiction.

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Glutamate transport in cultures from developing avian cerebellum: Presence of GLT-1 immunoreactivity in Purkinje neurons

Cited by 24 publications

References 44 publications

Neuronal vs glial glutamate uptake: Resolving the conundrum

Neuronal vs glial glutamate uptake: Resolving the conundrum

Molecular Pharmacology of the Na+-Dependent Transport of Acidic Amino Acids in the Mammalian Central Nervous System.

GLAST But Not Least—Distribution, Function, Genetics and Epigenetics of l-Glutamate Transport in Brain—Focus on GLAST/EAAT1

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