Effects of glucose deficiency on glutamate/aspartate release and excitatory synaptic responses in the hippocampal CA1 area in vitro

Sp, Burke; Nadler, J. Victor

doi:10.1016/0006-8993(89)90329-6

Cited by 33 publications

(19 citation statements)

References 42 publications

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“…In fact, during glucose deprivation both inhibition of excitatory transmission and membrane hyperpolarization have been reported in hippocampus (Bachelard et al, 1984;Spuler et al, 1988;Burke and Nadler, 1989;Knopfel et al, 1990;Crepel et al, 1992) and in the dorsolateral septal nucleus (Shoji, 1992). We found that brief periods (5-10 min) of aglycemia, as well as exogenous adenosine, selectively cause presynaptic inhibition in the striatum.…”

Section: Comparison With Other Studiesmentioning

confidence: 58%

“…Depression of excitatory synaptic transmission during aglycemia has been reported in different brain areas (Bachelard et al, 1984;Burke and Nadler, 1989;Crepel et al, 1992;Shoji, 1992). This decrease might be produced by different mechanisms: (1) a reduction in the release of excitatory amino acids from the synaptic terminals, (2) an alteration of postsynaptic glutamate receptors, and (3) an abnormal coupling of postsynaptic receptors with synaptic conductances.…”

Section: Abstract: Adenosine; Aglycemia; Ischemia; Excitatory Amino mentioning

confidence: 99%

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Endogenous Adenosine Mediates the Presynaptic Inhibition Induced by Aglycemia at Corticostriatal Synapses

et al. 1997

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Energy deprivation, as a result of aglycemia, leads to depression of the central synaptic transmission. Endogenous adenosine has been implicated in this depressant effect. We have studied the possible involvement of endogenous adenosine in the depression of corticostriatal excitatory transmission induced by glucose deprivation by using intracellular recordings in brain slices. After stimulation of corticostriatal fibers, EPSPs were recorded from striatal spiny neurons. Adenosine (3-300 M) or brief periods (5-10 min) of aglycemia reduced the EPSP amplitude but did not alter the membrane potential and the resistance of the recorded cells. These inhibitory effects were not associated with an alteration of the postsynaptic sensitivity to exogenous glutamate but were coupled with an increased paired-pulse facilitation, suggesting the involvement of presynaptic mechanisms. A delayed postsynaptic membrane depolarization/inward current was detected after 15-20 min of glucose deprivation. The presynaptic inhibitory effects induced by adenosine and aglycemia were both antagonized either by the nonselective adenosine receptor antagonist caffeine (2.5 mM) or by the A1 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 M) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nM). Conversely, these antagonists affected neither the delayed membrane depolarization/inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers tolbutamide (1 mM) and glipizide (100 nM) had no effect on the aglycemia-induced decrease of EPSP amplitude. Our data demonstrate that endogenous adenosine acting on A1 receptors mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses, whereas ATP-dependent potassium channels do not play a significant role in this presynaptic inhibition.

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Section: Comparison With Other Studiesmentioning

confidence: 58%

Section: Abstract: Adenosine; Aglycemia; Ischemia; Excitatory Amino mentioning

confidence: 99%

Endogenous Adenosine Mediates the Presynaptic Inhibition Induced by Aglycemia at Corticostriatal Synapses

et al. 1997

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“…L-aspartate has been shown to be released in a Ca 2+ and clostridium toxin sensitive manner from various in vitro brain preparations (e.g. [1][2][3][4][5][6][7]). Strongly in favour of an exocytotic release mechanism are our previous immunocytochemical results showing that K + induced depolarisation elicited depletion of L-aspartate from nerve endings, which could be inhibited by low extracellular Ca 2+ -concentrations and tetanus toxin [8][9][10].…”

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confidence: 99%

Vesicular Release of L- and D-Aspartate from Hippocampal Nerve Terminals: Immunogold Evidence~!2008-09-01~!2008-10-15~!2008-12-05~!

Holten¹,

Morland²,

Nordengen³

et al. 2008

TONEURJ

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Abstract:Glutamate is established as the most important excitatory transmitter in the brain. The transmitter status of aspartate is debated. There is evidence that aspartate is released from nerve terminals by exocytosis. However, release through excitatory amino acid transporters (EAATs) could be an alternative mechanism. We further investigated this by use of light and quantitative electron microscopic immunocytochemistry. The nerve terminal localisation of aspartate was compared to that of glutamate using antibodies specifically recognising the amino acids. Rat hippocampal slices were incubated under normal (3 mM) and depolarising (55 mM) concentrations of K + with and without the excitatory amino acid transporter inhibitor threo-beta-benzyloxyaspartate (TBOA). If aspartate is released either through reversal of the EAATs or through exchange with synaptically released glutamate, we would expect that TBOA would block the depolarisation induced release of aspartate. We found, however, that there was a substantial depletion of aspartate, as well as of glutamate, from hippocampal nerve terminals during K + induced depolarisation in the presence of TBOA. The possibility that aspartate is released through exocytosis from synaptic vesicles was further investigated by the use of a D-aspartate uptake assay, including exposure of the slices to exogenous D-aspartate and the use of D-aspartate immunogold cytochemistry to localise D-aspartate in the fixed tissue. We found that D-aspartate taken up into the terminals was concentrated in synaptic vesicles as opposed to in the cytoplasmic matrix. This is in line with the presence in synaptic vesicles of the recently identified vesicular transporter for aspartate.Keywords: Synaptic vesicles, immunocytochemistry, amino acids, electron microscopy, transport.The release of glutamate at synapses in the brain is well studied. Glutamate is released upon depolarisation of the presynaptic nerve terminal, leading to opening of voltage gated Ca 2+ channels and Ca 2+-dependent fusion of glutamate filled synaptic vesicles with the plasma membrane. The mechanism of release of L-aspartate at central synapses remains less defined. L-aspartate has been shown to be released in a Ca 2+ and clostridium toxin sensitive manner from various in vitro brain preparations (e.g. [1][2][3][4][5][6][7]). Strongly in favour of an exocytotic release mechanism are our previous immunocytochemical results showing that K + induced depolarisation elicited depletion of L-aspartate from nerve endings, which could be inhibited by low extracellular Ca 2+ -concentrations and tetanus toxin [8][9][10]. In addition, Daspartate has been shown to be subject to exocytotic release both from cultured neurons [11] There is ample evidence that excitatory nerve endings in the brain contain functional plasma membrane excitatory amino acid transporters (EAATs) [16][17][18][19][20]. The previous aspartate release data do not clearly distinguish between Laspartate release via exocytosis and via these EAATs, which could release as...

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“…In those pathways, aspartate immunoreactivity was associated with synaptic vesicles to the same degree as glutamate or GABA immunoreactivity. Aspartate is coreleased with glutamate from the Schaffer collateral-commissural and dentate gyrus associationalcommissural pathways in a Ca 2+ -dependent manner [2,3,19] and could serve as a co-transmitter through its selective activation of NMDA receptors [4,22]. However, the mechanism of aspartate release appears to differ in some respects from that of the recognized amino acid transmitters.…”

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confidence: 99%

Reduced aspartate release from rat hippocampal synaptosomes loaded with Clostridial toxin light chain by electroporation: Evidence for an exocytotic mechanism

Wang

Nadler

2007

Neuroscience Letters

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Aspartate can be released from certain hippocampal pathways along with glutamate or GABA. Although aspartate immunoreactivity has been localized to synaptic vesicles and aspartate release is Ca 2+ -dependent, there has been no clear evidence favoring an exocytotic mechanism. In particular, pretreatment with Clostridial toxins has not consistently inhibited aspartate release, even when release of glutamate from the same tissue samples was markedly inhibited. To address this issue directly, rat hippocampal synaptosomes were permeabilized transiently by electroporation in the presence of active or inactivated Clostridial toxin light chains. Loading rat hippocampal synaptosomes with the active light chain of tetanus toxin or of botulinum neurotoxins A, B or C reduced the K + -evoked release of aspartate at least as much as that of glutamate. These results confirm that aspartate is released by exocytosis in rat hippocampus. KeywordsAspartate; Excitatory amino acids; Transmitter release; Hippocampus; Exocytosis; Clostridial toxins Although hippocampal preparations have long been known to release aspartate along with the recognized transmitters glutamate and GABA [18,19], the mechanism and physiological significance of aspartate release remain unclear. Aspartate immunoreactivity has been localized to synaptic vesicles of certain excitatory [10,11] and inhibitory [12] hippocampal pathways. In those pathways, aspartate immunoreactivity was associated with synaptic vesicles to the same degree as glutamate or GABA immunoreactivity. Aspartate is coreleased with glutamate from the Schaffer collateral-commissural and dentate gyrus associationalcommissural pathways in a Ca 2+ -dependent manner [2,3,19] and could serve as a co-transmitter through its selective activation of NMDA receptors [4,22]. However, the mechanism of aspartate release appears to differ in some respects from that of the recognized amino acid transmitters. In our previous study of rat hippocampal synaptosomes, aspartate release was more sensitive than glutamate release to increases in intracellular [Ca 2+ ] outside the presynaptic active zones, was reduced by KB-R7943, an inhibitor of Na + /Ca 2+ exchange, was much less sensitive than glutamate release to block of P/Q-type voltage-dependent Ca 2+ channels, and resisted both bafilomycin A 1 , an inhibitor of vacuolar H + -ATPase, and Clostridial toxins [1].Address correspondence to J. Victor Nadler, Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA. Telephone: (919) 684-5317; FAX: (919) 681-8609; E-mail: nadle002@acpub.duke.edu.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could af...

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Effects of glucose deficiency on glutamate/aspartate release and excitatory synaptic responses in the hippocampal CA1 area in vitro

Cited by 33 publications

References 42 publications

Endogenous Adenosine Mediates the Presynaptic Inhibition Induced by Aglycemia at Corticostriatal Synapses

Endogenous Adenosine Mediates the Presynaptic Inhibition Induced by Aglycemia at Corticostriatal Synapses

Vesicular Release of L- and D-Aspartate from Hippocampal Nerve Terminals: Immunogold Evidence~!2008-09-01~!2008-10-15~!2008-12-05~!

Reduced aspartate release from rat hippocampal synaptosomes loaded with Clostridial toxin light chain by electroporation: Evidence for an exocytotic mechanism

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