title: Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.
abstract: A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.
authors.affiliation: Department of Genetics, National Institute of Psychiatry "Ramón de la Fuente Muñiz" (INPRFM), Mexico DF, Mexico.
authors.forename: G A
authors.initials: GA
authors.lastname: Martínez-Levy
authors.affiliation: Department of Pharmacobiology, Center for Research and Advanced Studies (CINVESTAV), Mexico City, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Rocha
authors.affiliation: Department of Neurobiology, Lubin Lab, University at Birmingham in Alabama, USA.
authors.forename: F D
authors.initials: FD
authors.lastname: Lubin
authors.affiliation: Neurosurgery Section, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" (INNNMVS), Mexico City, Mexico.
authors.forename: M A
authors.initials: MA
authors.lastname: Alonso-Vanegas
authors.affiliation: Department of Genetics, National Institute of Psychiatry "Ramón de la Fuente Muñiz" (INPRFM), Mexico DF, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Nani
authors.affiliation: Neurosurgery Section, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" (INNNMVS), Mexico City, Mexico.
authors.forename: R M
authors.initials: RM
authors.lastname: Buentello-García
authors.affiliation: Institute of Cell Physiology, National University of Mexico, UNAM, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Molina
authors.affiliation: Department of Genetics, National Institute of Psychiatry "Ramón de la Fuente Muñiz" (INPRFM), Mexico DF, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Briones-Velasco
authors.affiliation: Institute of Cell Physiology, National University of Mexico, UNAM, Mexico City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Recillas-Targa
authors.affiliation: Department of Genetics, National Institute of Psychiatry "Ramón de la Fuente Muñiz" (INPRFM), Mexico DF, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Pérez-Molina
authors.affiliation: Clinical Research Department, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" (INNNMVS), Mexico City, Mexico.
authors.forename: D
authors.initials: D
authors.lastname: San-Juan
authors.affiliation: Neurosurgery Section, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" (INNNMVS), Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Cienfuegos
authors.affiliation: Department of Genetics, National Institute of Psychiatry "Ramón de la Fuente Muñiz" (INPRFM), Mexico DF, Mexico. Electronic address: cruz@imp.edu.mx.
authors.forename: C S
authors.initials: CS
authors.lastname: Cruz-Fuentes
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D019175:DNA Methylation; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000235:genetics*; D005091:Exons; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020280:Sertraline / Q000627:therapeutic use; D000077236:Topiramate; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D000077236:Topiramate; D005632:Fructose; C579455:BDNF protein, human; D020280:Sertraline
keywords: BDNF; epigenetics; human; mRNA expression; pharmaco-resistant temporal lobe epilepsy; promoter methylation