PMID- 15668432
OWN - NLM
STAT- MEDLINE
DCOM- 20050920
LR  - 20151119
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 64
IP  - 2
DP  - 2005 Jan 25
TI  - Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal 
      lobe epilepsy.
PG  - 326-33
AB  - BACKGROUND: Increased levels of glutamate have been reported in the epileptogenic 
      hippocampus of patients with temporal lobe epilepsy (TLE). This sustained 
      increase, which may contribute to the initiation and propagation of seizure 
      activity, indicates impaired clearance of glutamate released by neurons. 
      Glutamate is predominantly cleared by glial cells through the excitatory amino 
      acid transporter 2 (EAAT2) and its subsequent conversion to glutamine by the 
      glial enzyme glutamine synthetase (GS). METHODS: The authors examined the 
      hippocampal distribution of GS, EAAT2, and glial fibrillary acidic protein (GFAP) 
      by immunohistochemistry in TLE patients with (HS group) and without hippocampal 
      sclerosis (non-HS group), and in autopsy controls. In hippocampal homogenates the 
      authors measured relative protein amounts by immunoblotting and GS enzyme 
      activity. RESULTS: In the autopsy control and non-HS group GS immunoreactivity 
      (IR) was predominantly found in glia in the neuropil of the subiculum, of the 
      pyramidal cell layer of all CA fields, and in the supragranular layer of the 
      dentate gyrus. In the HS group, GS and EAAT2 IR were markedly reduced in 
      subfields showing neuron loss (CA1 and CA4), whereas GFAP IR was increased. The 
      reduction in GS IR in the HS group was confirmed by immunoblotting and paralleled 
      by decreased GS enzyme activity. CONCLUSIONS: Glial glutamine synthetase is 
      downregulated in the hippocampal sclerosis (HS) hippocampus of temporal lobe 
      epilepsy (TLE) patients in areas with severe neuron loss. This downregulation 
      appears to be pathology-related, rather than seizure-related, and may be part of 
      the mechanism underlying impaired glutamate clearance found in the hippocampus of 
      TLE patients with HS.
FAU - van der Hel, W S
AU  - van der Hel WS
AD  - Department of Pharmacology & Anatomy, Rudolf Magnus Institute of Neuroscience, 
      University Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Notenboom, R G E
AU  - Notenboom RG
FAU - Bos, I W M
AU  - Bos IW
FAU - van Rijen, P C
AU  - van Rijen PC
FAU - van Veelen, C W M
AU  - van Veelen CW
FAU - de Graan, P N E
AU  - de Graan PN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Anticonvulsants)
RN  - 0 (Biomarkers)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 6.3.1.2 (Glutamate-Ammonia Ligase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anterior Temporal Lobectomy
MH  - Anticonvulsants/therapeutic use
MH  - Biomarkers
MH  - Brain Neoplasms/enzymology
MH  - Cell Death
MH  - Combined Modality Therapy
MH  - Epilepsy, Temporal Lobe/drug therapy/*enzymology/pathology/surgery
MH  - Excitatory Amino Acid Transporter 2/analysis
MH  - Female
MH  - Glial Fibrillary Acidic Protein/analysis
MH  - Glutamate-Ammonia Ligase/analysis/*deficiency
MH  - Glutamic Acid/metabolism
MH  - Hippocampus/*enzymology/pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neuroglia/enzymology
MH  - Neurons/*pathology
MH  - Sclerosis
EDAT- 2005/01/26 09:00
MHDA- 2005/09/21 09:00
CRDT- 2005/01/26 09:00
PHST- 2005/01/26 09:00 [pubmed]
PHST- 2005/09/21 09:00 [medline]
PHST- 2005/01/26 09:00 [entrez]
AID - 64/2/326 [pii]
AID - 10.1212/01.WNL.0000149636.44660.99 [doi]
PST - ppublish
SO  - Neurology. 2005 Jan 25;64(2):326-33. doi: 10.1212/01.WNL.0000149636.44660.99.