title: Large-scale expression study of human mesial temporal lobe epilepsy: evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex.
abstract: Human mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent pharmacoresistance. The molecular alterations underlying human MTLE remain poorly understood. A two-step transcriptional analysis consisting in cDNA microarray experiments followed by quantitative RT-PCR validations was performed. Because the entorhinal cortex (EC) plays an important role in the pathophysiology of the MTLE and usually discloses no detectable or little cell loss, resected EC and each corresponding lateral temporal neocortex (LTC) of MTLE patients were used as the source of disease-associated and control RNAs, respectively. Six genes encoding (i) a serotonin receptor (HTR2A) and a neuropeptide Y receptor type 1 (NPY1R), (ii) a protein (FHL2) associating with the KCNE1 (minK) potassium channel subunit and with presenilin-2 and (iii) three immune system-related proteins (C3, HLA-DR-gamma and CD99), were found consistently downregulated or upregulated in the EC of MTLE patients as compared with non-epileptic autopsy controls. Quantitative western blot analyses confirmed decreased expression of NPY1R in all eight MTLE patients tested. Immunohistochemistry experiments revealed the existence of a perivascular infiltration of C3 positive leucocytes and/or detected membrane attack complexes on a subset of neurons, within the EC of nine out of eleven MTLE patients. To summarize, a large-scale microarray expression study on the EC of MTLE patients led to the identification of six candidate genes for human MTLE pathophysiology. Altered expression of NPY1R and C3 was also demonstrated at the protein level. Overall, our data indicate that local dysregulation of the neurotransmission and complement systems in the EC is a frequent event in human MTLE.
authors.affiliation: INSERM UMR 491, Université de la Méditerranée, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jamali
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bartolomei
authors.forename: Andrée
authors.initials: A
authors.lastname: Robaglia-Schlupp
authors.forename: Annick
authors.initials: A
authors.lastname: Massacrier
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Peragut
authors.forename: Jean
authors.initials: J
authors.lastname: Régis
authors.forename: Henri
authors.initials: H
authors.lastname: Dufour
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Patrice
authors.initials: P
authors.lastname: Roll
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pereira
authors.forename: Barbara
authors.initials: B
authors.lastname: Royer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Roeckel-Trevisiol
authors.forename: Marc
authors.initials: M
authors.lastname: Fontaine
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.forename: José
authors.initials: J
authors.lastname: Boucraut
authors.forename: Patrick
authors.initials: P
authors.lastname: Chauvel
authors.forename: Pierre
authors.initials: P
authors.lastname: Cau
authors.forename: Pierre
authors.initials: P
authors.lastname: Szepetowski
mesh_terms: D000328:Adult; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D015938:Complement Membrane Attack Complex; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D018728:Entorhinal Cortex / Q000276:immunology / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation
chemical_list: D003176:Complement C3; D015938:Complement Membrane Attack Complex; D018377:Neurotransmitter Agents; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor