PMID- 18620031
OWN - NLM
STAT- MEDLINE
DCOM- 20090206
LR  - 20211020
IS  - 0306-4522 (Print)
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 155
IP  - 4
DP  - 2008 Sep 9
TI  - Selective overexpression of excitatory amino acid transporter 2 (EAAT2) in 
      astrocytes enhances neuroprotection from moderate but not severe 
      hypoxia-ischemia.
PG  - 1204-11
LID - 10.1016/j.neuroscience.2008.05.059 [doi]
AB  - Attempts have been made to elevate excitatory amino acid transporter 2 (EAAT2) 
      expression in an effort to compensate for loss of function and expression 
      associated with disease or pathology. Increased EAAT2 expression has been noted 
      following treatment with beta-lactam antibiotics, and during ischemic 
      preconditioning (IPC). However, both of these conditions induce multiple changes 
      in addition to alterations in EAAT2 expression that could potentially contribute 
      to neuroprotection. Therefore, the aim of this study was to selectively 
      overexpress EAAT2 in astrocytes and characterize the cell type specific 
      contribution of this transporter to neuroprotection. To accomplish this we used a 
      recombinant adeno-associated virus vector, AAV1-glial fibrillary acidic protein 
      (GFAP)-EAAT2, designed to selectively drive the overexpression of EAAT2 within 
      astrocytes. Both viral-mediated gene delivery and beta-lactam antibiotic 
      (penicillin-G) treatment of rat hippocampal slice cultures resulted in a 
      significant increase in both the expression of EAAT2, and dihydrokainate (DHK) 
      sensitive glutamate uptake. Penicillin-G provided significant neuroprotection in 
      rat hippocampal slice cultures under conditions of both moderate and severe 
      oxygen glucose deprivation (OGD). In contrast, viral-mediated overexpression of 
      EAAT2 in astrocytes provided enhanced neuroprotection only following a moderate 
      OGD insult. These results indicate that functional EAAT2 can be selectively 
      overexpressed in astrocytes, leading to enhanced neuroprotection. However, this 
      cell type specific increase in EAAT2 expression offers only limited protection 
      compared to treatment with penicillin-G.
FAU - Weller, M L
AU  - Weller ML
AD  - NIH COBRE Center for Structural and Functional Neuroscience, Department of 
      Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 
      59812, USA. wellerm@mail.nih.gov
FAU - Stone, I M
AU  - Stone IM
FAU - Goss, A
AU  - Goss A
FAU - Rau, T
AU  - Rau T
FAU - Rova, C
AU  - Rova C
FAU - Poulsen, D J
AU  - Poulsen DJ
LA  - eng
GR  - P20 RR015583-060008/RR/NCRR NIH HHS/United States
GR  - P20 RR015583/RR/NCRR NIH HHS/United States
GR  - P20 RR15583/RR/NCRR NIH HHS/United States
GR  - P20 RR017670/RR/NCRR NIH HHS/United States
GR  - R21 NS058541/NS/NINDS NIH HHS/United States
GR  - R21 NS058541-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080617
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Penicillins)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenoviridae/physiology
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/*metabolism
MH  - Cell Line, Transformed
MH  - Excitatory Amino Acid Transporter 2/genetics/*metabolism
MH  - Gene Expression/drug effects/genetics/*physiology
MH  - Glial Fibrillary Acidic Protein/genetics/metabolism
MH  - Glucose/*deficiency
MH  - Glutamic Acid/metabolism
MH  - Hippocampus/cytology
MH  - Humans
MH  - Hypoxia/*prevention & control
MH  - In Vitro Techniques
MH  - Penicillins/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Transfection/methods
PMC - PMC2729515
MID - NIHMS69674
EDAT- 2008/07/16 09:00
MHDA- 2009/02/07 09:00
PMCR- 2009/09/09
CRDT- 2008/07/16 09:00
PHST- 2008/04/21 00:00 [received]
PHST- 2008/05/26 00:00 [accepted]
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2009/02/07 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
PHST- 2009/09/09 00:00 [pmc-release]
AID - S0306-4522(08)00836-1 [pii]
AID - 10.1016/j.neuroscience.2008.05.059 [doi]
PST - ppublish
SO  - Neuroscience. 2008 Sep 9;155(4):1204-11. doi: 10.1016/j.neuroscience.2008.05.059. 
      Epub 2008 Jun 17.