title: Multireceptor analysis in human neocortex reveals complex alterations of receptor ligand binding in focal epilepsies.
abstract: OBJECTIVE
  A disturbed balance between excitatory and inhibitory neurotransmission underlies epileptic activity, although reports concerning neurotransmitter systems involved remain controversial.
  
  
  METHODS
  We quantified densities of 15 receptors in neocortical biopsies from patients with pharmacoresistant focal temporal lobe epilepsy and autopsy controls, and searched for correlations between density alterations and clinical factors or the occurrence of spontaneous synaptic potentials in vitro.
  
  
  RESULTS
  α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-d-aspartate (NMDA), peripheral benzodiazepine, muscarinic (M)(1) , M(2) , nicotinic, α(1) , α(2h) , serotonin (5-HT)(1A) , and adenosine (A)(1) receptor densities were significantly altered in biopsies. The epileptic cohort was subdivided based on clinical (febrile seizures, hippocampal sclerosis, neocortical pathologies, surgery outcome) or electrophysiologic (spontaneous field potentials) criteria, resulting in different patterns of significantly altered receptor types when comparing a given epileptic group with controls. Only AMPA, kainate, M(2) , and 5-HT(1A) receptors were always significantly altered. γ-Aminobutyric acid (GABA)(A) , GABA(B) , and 5-HT(2) receptor alterations were never significant. Correlation patterns between receptor alterations and illness duration or seizure frequency varied depending on whether the epileptic cohort was considered as a whole or subdivided.
  
  
  CONCLUSIONS
  Neocortical temporal lobe epilepsy is associated with a generalized receptor imbalance resulting in a net potentiation of excitatory neurotransmission. Peripheral benzodiazepine receptor alterations highlight that astrocytes are also impaired by seizure activity.
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-2), Research Center Jülich, Jülich, Germany. n.palomero-gallagher@fz-juelich.de
authors.forename: Nicola
authors.initials: N
authors.lastname: Palomero-Gallagher
authors.forename: Axel
authors.initials: A
authors.lastname: Schleicher
authors.forename: Hans-J
authors.initials: HJ
authors.lastname: Bidmon
authors.forename: Heinz-W
authors.initials: HW
authors.lastname: Pannek
authors.forename: Volkmar
authors.initials: V
authors.lastname: Hans
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
authors.forename: Erwin-J
authors.initials: EJ
authors.lastname: Speckmann
authors.forename: Karl
authors.initials: K
authors.lastname: Zilles
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004569:Electroencephalography / Q000379:methods; D004828:Epilepsies, Partial / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055815:Young Adult
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface