DOWNREGULATION OF GLUTAMINE SYNTHETASE IN THE HUMAN EPILEPTOGENIC HIPPOCAMPUS DESPITE GLIAL PROLIFERATION- A KEY TO SUSTAINED LEVELS OF GLUTAMATE DURING SEIZURES?
Abstract number :
3.039
Submission category :
Year :
2002
Submission ID :
1364
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Tore Eid, Marion J. Thomas, Dennis D. Spencer, Ole P. Ottersen, Nihal C. de Lanerolle. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT; Department of Anatomy, University of Oslo, Oslo, Norway
RATIONALE: Increased ictal concentrations of extracellular glutamate have been demonstrated by in vivo microdialysis in the epileptogenic hippocampus compared to the non-epileptogenic hippocampus in patients with mesial temporal lobe epilepsy (MTLE). In the present study we explored the possibility that the elevated levels of glutamate in MTLE could be due to a downregulation of the glutamate-detoxifying enzyme, glutamine synthetase (GS) in astrocytes in the epileptogenic hippocampus.
METHODS: Sclerotic (MTLE) and non-sclerotic human hippocampi were obtained from neurosurgical treatment of drug-resistant temporal lobe epilepsy. After surgery the tisse was immersion fixed, sectioned and immunostained for GS. The pattern of immunostaining in sclerotic hippocampi (where the seizure focus resides in the hippocampus) were compared to that of non-sclerotic hippocampi (where the seizure focus is not in the hippocampus).
RESULTS: GS staining was found in astrocytes in both sclerotic and non-sclerotic hippocampi. In the sclerotic hippocampi the Ammon[ssquote]s horn was characterized by neuronal loss and glial proliferation, especially in area CA1. However, in the glia in the sclerotic area CA1 and to a lesser degree in the hilus, the expression of GS was markedly reduced. In contrast, in the non-sclerotic hippocampi, numerous GS-positive glial cells were present thoughout all hippocampal subfields.
CONCLUSIONS: This observation supports the hypothesis that a deficiency of GS may underlie the ictal accumulation of glutamate in the epileptogenic hippocampus in MTLE.
[Supported by: NIH grant P01 NS39092-01]