title: Differential glutamate dehydrogenase (GDH) activity profile in patients with temporal lobe epilepsy.
abstract: OBJECTIVE
  Pathophysiologic mechanisms underlying temporal lobe epilepsy (TLE) are still poorly understood. One major hypothesis links alterations in energy metabolism to glutamate excitotoxicity associated with seizures in TLE. The purpose of this study was to determine whether changes in the activities of enzymes critical in energy and neurotransmitter metabolism contributed to the alterations in metabolic status leading to the excitotoxic effects of glutamate.
  
  
  METHODS
  Activities of four key enzymes involved in energy metabolism and glutamate cycling in the brain [aspartate aminotransferase (AAT), citrate synthase (CS), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH)] were measured in anterolateral temporal neocortical and hippocampal tissues obtained from three different groups of medically intractable epilepsy patients having either mesial, paradoxical, or mass lesion-associated temporal lobe epilepsy (MTLE, PTLE, MaTLE), respectively.
  
  
  RESULTS
  We found that GDH activity was significantly decreased in the temporal cortex mainly in the MTLE group. A similar trend was recognized in the hippocampus of the MTLE. In all three patient groups, GDH activity was considerably lower, and AAT and LDH activities were higher in cortex of MTLE as compared with the corresponding activities in hippocampus (p<0.05). In the MTLE cortex and hippocampus, GDH activities were negatively correlated with the duration since the first intractable seizure.
  
  
  CONCLUSIONS
  Our results support the hypothesis suggesting major alteration in GDH activity mainly in the MTLE group. It is proposed that significant alterations in the enzyme activities may be contributing to decreased metabolism of glutamate, leading to its accumulation.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello, Idaho 83209, USA.
authors.forename: Gauri H
authors.initials: GH
authors.lastname: Malthankar-Phatak
authors.forename: Nihal
authors.initials: N
authors.lastname: de Lanerolle
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Spencer
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Behar
authors.forename: Susan S
authors.initials: SS
authors.lastname: Spencer
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: James C K
authors.initials: JC
authors.lastname: Lai
mesh_terms: D000293:Adolescent; D000328:Adult; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002648:Child; D003937:Diagnosis, Differential; D004734:Energy Metabolism; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000201:enzymology* / Q000378:metabolism; D013702:Temporal Lobe / Q000201:enzymology* / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases