title: Gene expression of glutamate metabolizing enzymes in the hippocampal formation in human temporal lobe epilepsy.
abstract: OBJECTIVE
  Increased interictal concentrations of extracellular hippocampal glutamate have been implicated in the pathophysiology of temporal lobe epilepsy (TLE). Recent studies suggest that perturbations of the glutamate metabolizing enzymes glutamine synthetase (GS) and phosphate activated glutaminase (PAG) may underlie the glutamate excess in TLE. However, the molecular mechanism of the enzyme perturbations remains unclear. A better understanding of the regulatory mechanisms of GS and PAG could facilitate the discovery of novel therapeutics for TLE.
  
  
  METHODS
  We used in situ hybridization on histologic sections to assess the distribution and quantity of messenger RNA (mRNA) for GS and PAG in subfields of hippocampal formations from the following: (1) patients with TLE and concomitant hippocampal sclerosis, (2) patients with TLE and no hippocampal sclerosis, and (3) nonepilepsy autopsy subjects.
  
  
  RESULTS
  GS mRNA was increased by ~50% in the CA3 in TLE patients without hippocampal sclerosis versus in TLE patients with sclerosis and in nonepilepsy subjects. PAG mRNA was increased by >100% in the subiculum in both TLE patient categories versus in nonepilepsy subjects. PAG mRNA was also increased in the CA1, CA2, CA3, and dentate hilus in TLE without hippocampal sclerosis versus in TLE with sclerosis. Finally, PAG mRNA was increased in the dentate gyrus in TLE with sclerosis versus in nonepilepsy subjects, and also increased in the hilus in TLE without sclerosis versus in TLE with sclerosis.
  
  
  CONCLUSIONS
  These findings demonstrate complex changes in the expression of mRNAs for GS and PAG in the hippocampal formation in TLE, and raise the possibility that both transcriptional and posttranscriptional mechanisms may underlie the regulation of GS and PAG proteins in the epileptic brain.
authors: Departments of Laboratory Medicine Psychiatry Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8035, USA. tore.eid@yale.edu
authors: Tore
authors: T
authors: Eid
authors: Tih-Shih W
authors: TS
authors: Lee
authors: Yue
authors: Y
authors: Wang
authors: Edgar
authors: E
authors: Perez
authors: Edgar
authors: E
authors: Peréz
authors: Jana
authors: J
authors: Drummond
authors: Fredrik
authors: F
authors: Lauritzen
authors: Linda H
authors: LH
authors: Bergersen
authors: James H
authors: JH
authors: Meador-Woodruff
authors: Dennis D
authors: DD
authors: Spencer
authors: Nihal C
authors: NC
authors: de Lanerolle
authors: Robert E
authors: RE
authors: McCullumsmith
mesh_terms: D000293:Adolescent; D000328:Adult; D001344:Autopsy; D002648:Child; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics* / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D018698:Glutamic Acid; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase
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