title: Alterations of 5-HT1A receptor-induced G-protein functional activation and relationship to memory deficits in patients with pharmacoresistant temporal lobe epilepsy.
abstract: The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron emission tomography (PET) studies in patients with mesial temporal lobe epilepsy (mTLE) have demonstrated that a decrease in 5-HT1A receptor binding in temporal regions may play a role in memory impairment. The evidences lead us to speculate whether this decrease in receptor binding is associated with a reduced receptor number or if the functionality of the 5-HT1A receptor-induced G-protein activation and/or the second messenger cascade is modified. The purpose of the present study is to determine 5-HT1A receptor-induced G-protein functional activation by 8-OH-DPAT-stimulated [(35)S]GTPγS binding assay in hippocampal tissue of surgical patients with mTLE. We correlate functional activity with epilepsy history and neuropsychological assessment of memory. We found that maximum functional activation stimulation values (Emax) of [(35)S]GTPγS binding were significantly increased in mTLE group when compared to autopsy samples. Furthermore, significant correlations were found: (1) positive coefficients between the Emax with the age of patient and frequency of seizures; (2) negative coefficients between the Emax and working memory, immediate recall and delayed recall memory tasks. Our data suggest that the epileptic hippocampus of patients with mTLE presents an increase in 5-HT1A receptor-induced G-protein functional activation, and that this altered activity is related to age and seizure frequency, as well as to memory consolidation deficit.
authors.affiliation: Epilepsy Clinic, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico. Electronic address: manolacuellar@yahoo.com.mx.
authors.forename: Manola
authors.initials: M
authors.lastname: Cuellar-Herrera
authors.affiliation: Epilepsy Clinic, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico. Electronic address: analuisav@yahoo.com.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Velasco
authors.affiliation: Epilepsy Clinic, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico. Electronic address: slanfe@prodigy.net.mx.
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.affiliation: Epilepsy Clinic, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico. Electronic address: davidtrejomartinez@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Trejo
authors.affiliation: National Institute of Neurology and Neurosurgery "Manuel Velasco Suarez", Mexico City, Mexico. Electronic address: alonsovanegasm@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Alonso-Vanegas
authors.affiliation: Epilepsy Clinic, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico. Electronic address: anb.uayak@gmail.com.
authors.forename: Avril
authors.initials: A
authors.lastname: Nuche-Bricaire
authors.affiliation: Epilepsy Clinic, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico. Electronic address: daruny@yahoo.com.
authors.forename: Daruni
authors.initials: D
authors.lastname: Vázquez-Barrón
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address: rguevara@unam.mx.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Guevara-Guzmán
authors.affiliation: Department of Pharmacobiology. Center of Research and Advanced Studies, Mexico City, Mexico. Electronic address: lrocha@cinvestav.mx.
authors.forename: Luisa
authors.initials: L
authors.lastname: Rocha
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C583518:HTR1A protein, human; D044282:Receptor, Serotonin, 5-HT1A; D019204:GTP-Binding Proteins
keywords: Epilepsy; Human tissue; Memory; Neuropsi; Serotonin; [(35)S]GTPγS