Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy
| Autor: | W. S. van der Hel, C.W.M. van Veelen, P.N.E. de Graan, Robbert G. E. Notenboom, Ineke W. M. Bos, P.C. van Rijen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.medical_specialty Glutamic Acid Hippocampus Biology Hippocampal formation Glutamate-Ammonia Ligase Glutamine synthetase Internal medicine Glial Fibrillary Acidic Protein medicine Humans Aged Neurons Hippocampal sclerosis Sclerosis Cell Death Glial fibrillary acidic protein Brain Neoplasms Dentate gyrus Glutamate receptor Middle Aged Anterior Temporal Lobectomy medicine.disease Combined Modality Therapy Glutamine Endocrinology Epilepsy Temporal Lobe Excitatory Amino Acid Transporter 2 nervous system biology.protein Anticonvulsants Female Neurology (clinical) Neuroglia Biomarkers |
| Zdroj: | Neurology. 64:326-333 |
| ISSN: | 1526-632X 0028-3878 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|