NEURONAL AND GLIAL GLUTAMATE CLEARENCE MECHANISMS IN HUMAN DYSMORPHIC AND BALLOON CELLS
Abstract number :
2.037
Submission category :
Year :
2005
Submission ID :
5341
Source :
www.aesnet.org
Presentation date :
12/3/2005 12:00:00 AM
Published date :
Dec 2, 2005, 06:00 AM
Authors :
1Jorge A. Gonzalez-Martinez, 1William E. Bingaman, and 2Imad M. Najm
Glutamate transporters (GLTs) may play an important role in the expression of the epileptogenesis. The absence of glial GLTs is associated with spontaneous seizures in knockout mice. Previous studies show increased neuronal GLts in human dysplastic (dysmorphic) neurons. The expression of glial and neuronal GLTs and glutamine synthetase (GS) in balloon cells (BCs) and BC-containing malformations of cortical development (MCD) has not been studied. Neocortical tissue resected from 5 patients with medically intractable focal epilepsy due to MCD who underwent extraoperative prolonged electrocorticographic (EcoG) recordings was studied. The expression of glial (GLT1/EAAT2) and neuronal (EAAT3, EAAC1) GLTs and GS proteins was studied in resected samples using immunohistochemistry (IHC) and western blotting techniques. In situ co-localization of the 2 GLTs and GS with neuronal and glial markers was performed. BC-containing MCD lesions did not exhibit ictal patterns upon prolonged extraoperative EcoG recordings. Western blot analyses showed an increased expression of GLT1/EAAT2 and GS in BC-containing (non-epileptic) regions as compared to adjacent dysplastic (epileptic) areas that are devoid of BCs. At the cellular level, there was a differential expression of glial and neuronal GLTs in BCs and dysplastic neurons: The majority of BCs highly expressed glial but not neuronal GLTs. On the other hand, dysplastic neurons showed increased IHC staining with neuronal EAAT3 but not with EAAT2/GLT1. Moreover, only GFAP positive BCs also expressed GS. There is a differential GLT expression in dysplastic and balloon cells. The presence of glial GLTs and GS in BCs and severely dysplastic but non-epileptic BC-containing regions suggests a possible antiepileptic role for BCs and is consistent with the reported increased epileptogenicity in GLT1-deficient animals. (Supported by K08-NS02046 and R21-NS42354 grants to Imad M. Najm from the National Institute of Health (National Institutes of Neurological Disorders and Stroke, NINDS).)