PMID- 18805467
OWN - NLM
STAT- MEDLINE
DCOM- 20090105
LR  - 20210108
IS  - 0306-4522 (Print)
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 157
IP  - 1
DP  - 2008 Nov 11
TI  - 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).
PG  - 80-94
LID - 10.1016/j.neuroscience.2008.08.043 [doi]
AB  - 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.
FAU - Furness, D N
AU  - Furness DN
AD  - Institute of Science and Technology in Medicine, Keele University, Keele, Staffs, 
      ST5 5BG, UK.
FAU - Dehnes, Y
AU  - Dehnes Y
FAU - Akhtar, A Q
AU  - Akhtar AQ
FAU - Rossi, D J
AU  - Rossi DJ
FAU - Hamann, M
AU  - Hamann M
FAU - Grutle, N J
AU  - Grutle NJ
FAU - Gundersen, V
AU  - Gundersen V
FAU - Holmseth, S
AU  - Holmseth S
FAU - Lehre, K P
AU  - Lehre KP
FAU - Ullensvang, K
AU  - Ullensvang K
FAU - Wojewodzic, M
AU  - Wojewodzic M
FAU - Zhou, Y
AU  - Zhou Y
FAU - Attwell, D
AU  - Attwell D
FAU - Danbolt, N C
AU  - Danbolt NC
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 NS051561/NS/NINDS NIH HHS/United States
GR  - R01 NS051561-03/NS/NINDS NIH HHS/United States
GR  - 1R01NS051561/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080827
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Slc1a2 protein, rat)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Aspartic Acid/metabolism/physiology
MH  - Astrocytes/*metabolism/ultrastructure
MH  - Cell Membrane/metabolism/ultrastructure
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Excitatory Amino Acid Transporter 2/genetics/*physiology
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/*cytology/*metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Electron
MH  - Microscopy, Immunoelectron
MH  - Neuroglia/physiology
MH  - Presynaptic Terminals/*metabolism/*physiology/ultrastructure
MH  - Rats
MH  - Rats, Wistar
MH  - Substrate Specificity
MH  - Synaptosomes/metabolism
PMC - PMC2775085
MID - NIHMS76207
EDAT- 2008/09/23 09:00
MHDA- 2009/01/06 09:00
PMCR- 2009/11/11
CRDT- 2008/09/23 09:00
PHST- 2007/02/04 00:00 [received]
PHST- 2008/08/07 00:00 [revised]
PHST- 2008/08/08 00:00 [accepted]
PHST- 2008/09/23 09:00 [pubmed]
PHST- 2009/01/06 09:00 [medline]
PHST- 2008/09/23 09:00 [entrez]
PHST- 2009/11/11 00:00 [pmc-release]
AID - S0306-4522(08)01192-5 [pii]
AID - 10.1016/j.neuroscience.2008.08.043 [doi]
PST - ppublish
SO  - Neuroscience. 2008 Nov 11;157(1):80-94. doi: 10.1016/j.neuroscience.2008.08.043. 
      Epub 2008 Aug 27.