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Multireceptor analysis in human neocortex reveals complex alterations of receptor ligand binding in focal epilepsies
Author(s) -
PalomeroGallagher Nicola,
Schleicher Axel,
Bidmon HansJ.,
Pannek HeinzW.,
Hans Volkmar,
Gorji Ali,
Speckmann ErwinJ.,
Zilles Karl
Publication year - 2012
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2012.03634.x
Subject(s) - kainate receptor , ampa receptor , neuroscience , epilepsy , hippocampal sclerosis , neurotransmission , glutamate receptor , excitatory postsynaptic potential , medicine , gabaa receptor , biology , inhibitory postsynaptic potential , receptor , endocrinology , temporal lobe
Summary Purpose: 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. Key Findings: 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. Significance: 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.