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Cited by 254Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismIon Transport and Channel Regulation

A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: New insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2)

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Furness, D.N., Dehnes, Y., Akhtar, A.Q., Rossi, D.J., Hamann, M., Grutle, N.J., Gundersen, V., Holmseth, S. +6 more·2008·Neuroscience
DOI 10.1016/j.neuroscience.2008.08.043PMC PMC2775085
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Abstract

The relative distribution of the excitatory amino acid transporter 2 (EAAT2) between synaptic terminals and astroglia, and the importance of EAAT2 for the uptake into terminals is still unresolved. Here we have used antibodies to glutaraldehyde-fixed d-aspartate to identify electron microscopically the sites of d-aspartate accumulation in hippocampal slices. About 3/4 of all terminals in the stratum radiatum CA1 accumulated d-aspartate-immunoreactivity by an active dihydrokainate-sensitive mechanism which was absent in EAAT2 glutamate transporter knockout mice. These terminals were responsible for more than half of all d-aspartate uptake of external substrate in the slices. This is unexpected as EAAT2-immunoreactivity observed in intact brain tissue is mainly associated with astroglia. However, when examining synaptosomes and slice preparations where the extracellular space is larger than in perfusion fixed tissue, it was confirmed that most EAAT2 is in astroglia (about 80%). Neither d-aspartate uptake nor EAAT2 protein was detected in dendritic spines. About 6% of the EAAT2-immunoreactivity was detected in the plasma membrane of synaptic terminals (both within and outside of the synaptic cleft). Most of the remaining immunoreactivity (8%) was found in axons where it was distributed in a plasma membrane surface area several times larger than that of astroglia. This explains why the densities of neuronal EAAT2 are low despite high levels of mRNA in CA3 pyramidal cell bodies, but not why EAAT2 in terminals account for more than half of the uptake of exogenous substrate by hippocampal slice preparations. This and the relative amount of terminal versus glial uptake in the intact brain remain to be discovered.

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  • SLC1A2 (GLT-1) is the principal mediator of extracellular L-glutamate uptake, predominantly expressed in astrocytes but also present in excitatory neuronal terminals.

    “SLC1A2 (also known as GLT-1) is the principal mediator of extracellular L-glutamate uptake, predominantly expressed in astrocytes but also present in excitatory neuronal terminals [106, 125].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [125]

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Authors
Furness, D. N., Dehnes, Y., Akhtar, A. Q., Rossi, D. J., Hamann, M., Grutle, N. J., Gundersen, V., Holmseth, S., Lehre, K. P., Ullensvang, K., Wojewodzic, M., Zhou, Y., Attwell, D., & Danbolt, N. C.
Affiliations
  • Keele University (GB)
  • University of Oslo (NO)
  • Oregon Health & Science University (US)
  • University of Leicester (GB)
  • Oslo University Hospital (NO)
  • University College London (GB)
Corresponding author
Danbolt, N.C.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2008-11
Volume
157
Issue
1
Pages
80-94
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2008.08.043
PMC
PMC2775085
OpenAlex
W2017349018
Cited by
254
References
0
Citations by year
2026: 9 · 2025: 17 · 2024: 20 · 2023: 10 · 2022: 10 · 2021: 21 · 2020: 23 · 2019: 12 · 2018: 16 · 2017: 11 · 2016: 15 · 2015: 10 · 2014: 11 · 2013: 13 · 2012: 16
FWCI
5.77
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Leicester Research Archive (University of Leicester) (submittedVersion)
Funders
  • Wellcome Trust
  • National Institute of Neurological Disorders and Stroke (R01NS051561)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
GLT-1, glutamate uptake, hippocampus, synaptic terminals, astrocytes, D-aspartate, synaptosomes, axons, dendritic spines, glutamate transporters
MeSH terms
Animals, Aspartic Acid, Astrocytes, Cell Membrane, Electrophoresis, Polyacrylamide Gel, Hippocampus, Immunohistochemistry, Male, Microscopy, Electron, Neuroglia, Substrate Specificity, Synaptosomes, Microscopy, Immunoelectron, Rats, Wistar, Presynaptic Terminals, Mice, Knockout, Glutamic Acid, Excitatory Amino Acid Transporter 2, Mice, Rats

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