Increases in EAAC1 Glutamate Transporter in Temporal Lobe Epilepsy and Focal Cortical Dysplasia
Abstract number :
E.08
Submission category :
Year :
2000
Submission ID :
1128
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Hong Jin, Peter Crino, Tatiana Rikhter, Michael B Robinson, Douglas A Coulter, Amy R Brooks-Kayal, Children's Hosp of Philadelphia, Philadelphia, PA; Univ of Pennsylvania, Philadelphia, PA; Univ of Pennsylvania and Children's Hosp of Phila, Philadelphia,
Rationale: Glutamate has been implicated as a neurotoxic agent in epilepsy. Extracellular glutamate levels are regulated primarily by sodium-dependent transport of glutamate into glia and neurons. We examined glutamate transporter (GLUTr) expression in dentate granule cells (DGCs) in a rat model of temporal lobe epilepsy (TLE), and in surgically resected tissue from patients with intractable epilepsy due to TLE or focal cortical dysplasia. Methods: Relative expression of mRNA for neuronal GLUTr EAAC1 and glial GLUTr GLT1 were evaluated in individual DGCs acutely isolated from control and pilocarpine-treated (pilo) rats before and after onset of TLE and from patients with TLE using single-cell aRNA amplification. Hippocampal slices from pilo and control rats, from surgical specimens from patients with TLE or cortical dysplasia, and postmortem human controls were probed with anti-EAAC1 antibodies to examine protein expression. Results: Relative expression of EAAC1 mRNA (normalized to ?-actin) was increased >2-fold 24 hours after pilo-induced status and >3-fold in chronically-epileptic pilo rats compared to controls (ANOVA p<0.01). Relative expression in DGCs from TLE patients was similar to that seen in pilo rat DGCs, and 3-fold greater than in control rat DGCs. Relative expression of GLT1 mRNA was very low and not different between groups. EAAC1 immunolabeling was qualitatively higher in DGCs of pilo rats compared to controls, and in TLE patients compared to post-mortem controls. EAAC1 labeling was also markedly higher in dysplastic neurons from patients with focal cortical dysplasia compared to normal control neurons. Conclusions: Rapid and long-lasting epilepsy-associated alterations in EAAC1 mRNA and protein expression occur in DGCs of rats with TLE. Increased EAAC1 immunolabeling is seen in epileptogenic tissue from humans with intractable epilepsy due to TLE and focal cortical dysplasia. These findings suggest that altered glutamate transport may occur in a variety of forms of epilepsy. Supported by NIH (NS38595 to ABK, K08 MH01658 to PC, NS-32403 to DAC), Epilepsy Foundation (ABK), and Esther and Joseph Klingenstein Fund (PC).