Multireceptor analysis in human neocortex reveals complex alterations of receptor ligand binding in focal epilepsies

作者：Palomero Gallagher Nicola^*; Schleicher Axel; Bidmon Hans J; Pannek Heinz W; Hans Volkmar; Gorji Ali; Speckmann Erwin J; Zilles Karl

来源：Epilepsia, 2012, 53(11): 1987-1997.

DOI：10.1111/j.1528-1167.2012.03634.x

• Temporal lobe epilepsy
• Human neocortex
• Neurotransmitter receptors
• Field potentials
• In vitro

Purpose: A disturbed balance between excitatory and inhibitory neurotransmission underlies epileptic activity, although reports concerning neurotransmitter systems involved remain controversial. %26lt;br%26gt;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. %26lt;br%26gt;Key Findings: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-D-aspartate (NMDA), peripheral benzodiazepine, muscarinic (M)(1), M-2, nicotinic, alpha(1), alpha(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-HT1A receptors were always significantly altered. gamma-Aminobutyric acid (GABA)(A), GABA(B), and 5-HT2 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. %26lt;br%26gt;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.

• 出版日期2012-11