Expression of NMDA Receptor Subtypes and Glutamate Transporter Proteins in Human Epileptogenic Neoplastic Tissue.
Abstract number :
2.054
Submission category :
Year :
2001
Submission ID :
2799
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
D.K. Lachhwani, MB, BS, MD., Neurology, Cleveland Clinic, Cleveland, OH; Z. Ying, MD, PhD, Neurology, Cleveland Clinic, Cleveland, OH; A. Boongird, MD, Neurology, Cleveland Clinic, Cleveland, OH; E. Wyllie, MD, Neurology, Cleveland Clinic, Cleveland, OH;
RATIONALE: The role of NR1 and NR2A-B receptor subtypes, as well as of the Glutamate transporter proteins in the expression of focal epileptogenesis, has been a subject of much postulation and debate recently. The co-expression of both - NR1 and NR2A-B, in dysplastic human epileptogenic cortex, has previously been demonstrated, suggesting a possible role of such a co-assembly in the generation of hyperexcitability in the dysplastic neurons. Glutamate transporter proteins are instrumental in removing excess glutamate from extracellular space and changes in their expression may be implicated in epileptogenesis. Furthermore, cell culture experiments show that astrocytic expression of glutamate transporters is influenced by neurons.
METHODS: We have examined specimens collected prospectively from tissue surrounding epileptogenic lesions in four patients. Three patients had a CNS neoplasm and one had a cavernous angioma. These specimens were analyzed semiquantitatively, by established immunocytochemical (ICC) techniques, for the expression of NMDA receptor subtypes (NR1 and NR2A-B), as well as glutamate transporter protein (GLT1). Additionally, ICC staining was also performed for Neuronal nuclear (NeuN) antigen and Glial fibrillary astrocytic protein (GFAP). The results were compared to those obtained on epileptogenic tissue resected from 2 patients with cortical dysplasia.
RESULTS: The co-expression of NR2/NR1 was significantly increased in tissue obtained from patients with CNS neoplasm and cavernous angioma, when compared to MCDs. The areas with increased gliosis, did not correspond to an increased presence of GLT1.
CONCLUSIONS: These results provide further evidence that increased co-expression of NR1/NR2 plays a role in epileptogenesis. This expression is more robust in epileptogenic neoplasms, as compared to MCDs. The differential decrease in GLT1 expression in glia surrounding epileptogenic neoplasms may be due to abnormal neuronal factors.
Support: This abstract summarizes work done without financial support of commercial interests.