title: Pharmacoresistant temporal lobe epilepsy modifies histamine turnover and H3 receptor function in the human hippocampus and temporal neocortex.
abstract: Experiments were designed to evaluate the tissue content of tele-methylhistamine (t-MeHA) and histamine as well as H3 receptor (H3 Rs) binding and activation of the heterotrimeric guanine nucleotide binding αi/o proteins (Gαi/o) coupled to these receptors in the hippocampus and temporal neocortex of patients (n = 10) with pharmacoresistant mesial temporal lobe epilepsy (MTLE). Patients with MTLE showed elevated tissue content of t-MeHA in the hippocampus. Analyses revealed that a younger age at seizure onset was correlated with a higher tissue content of t-MeHA, lower H3 R binding, and lower efficacy of Gαi/o protein activation in the hippocampus. We conclude that the hippocampus shows a reduction in the H3 R function associated with enhanced histamine. In contrast, the temporal neocortex displayed a high efficacy of H3 Rs Gαi/o protein activation that was associated with low tissue contents of histamine and t-MeHA. These results indicate an overactivation of H3 Rs leading to decreased histamine in the temporal neocortex. However, this situation was lessened in circumstances such as a longer duration of epilepsy or higher seizure frequency. It is concluded that decrease in H3 Rs function and enhanced levels of histamine may contribute to the epileptic activity in the hippocampus and temporal neocortex of patients with pharmacoresistant MTLE.
authors.affiliation: Departamentos de Farmacobiología y, Centro de Investigación y de Estudios Avanzados, Department of Pharmacobiology, Mexico City, Mexico.
authors.forename: Ivette
authors.initials: I
authors.lastname: Bañuelos-Cabrera
authors.affiliation: General Hospital of Mexico, Mexico City, Mexico.
authors.forename: Manola
authors.initials: M
authors.lastname: Cuéllar-Herrera
authors.affiliation: General Hospital of Mexico, Mexico City, Mexico.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Velasco
authors.affiliation: General Hospital of Mexico, Mexico City, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.affiliation: National Institute of Neurology and Neurosurgery, "Manuel Velasco Súrez", Mexico City, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Alonso-Vanegas
authors.affiliation: Departamentos de Farmacobiología y, Centro de Investigación y de Estudios Avanzados, Department of Pharmacobiology, Mexico City, Mexico.
authors.forename: Francia
authors.initials: F
authors.lastname: Carmona
authors.affiliation: Department of Physiology, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Guevara
authors.affiliation: Physiology, Biophysics and Neuroscience, Center of Research and Advanced Studies, Mexico City, Mexico.|del Centro de Investigación y de Estudios Avanzados, México DF, México.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Arias-Montaño
authors.affiliation: Departamentos de Farmacobiología y, Centro de Investigación y de Estudios Avanzados, Department of Pharmacobiology, Mexico City, Mexico.
authors.forename: Luisa
authors.initials: L
authors.lastname: Rocha
mesh_terms: D000328:Adult; D000069279:Drug Resistant Epilepsy / Q000378:metabolism* / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D019579:Neocortex / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D018100:Receptors, Histamine H3; D006632:Histamine
keywords: Gαi/o protein; H3 receptors; Histamine; Tele-methylhistamine; Temporal lobe epilepsy