Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy.

Abstract

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.

• Authors: W S van der Hel, R G E Notenboom, I W M Bos, P C van Rijen, C W M van Veelen, P N E de Graan
• Journal: Neurology (Neurology) Vol. 64 Issue 2 Pg. 326-33 (Jan 25 2005) ISSN: 1526-632X [Electronic] United States
• PMID: 15668432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Biomarkers
• Excitatory Amino Acid Transporter 2
• Glial Fibrillary Acidic Protein
• Glutamic Acid
• Glutamate-Ammonia Ligase

Topics

• Adult
• Aged
• Anterior Temporal Lobectomy
• Anticonvulsants (therapeutic use)
• Biomarkers
• Brain Neoplasms (enzymology)
• Cell Death
• Combined Modality Therapy
• Epilepsy, Temporal Lobe (drug therapy, enzymology, pathology, surgery)
• Excitatory Amino Acid Transporter 2 (analysis)
• Female
• Glial Fibrillary Acidic Protein (analysis)
• Glutamate-Ammonia Ligase (analysis, deficiency)
• Glutamic Acid (metabolism)
• Hippocampus (enzymology, pathology)
• Humans
• Male
• Middle Aged
• Neuroglia (enzymology)
• Neurons (pathology)
• Sclerosis