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Large-scale study of human drug-resistant mesial temporal lobe epilepsy Volume 19, issue 1, Janvier, Février, Mars 2007

Authors
Inserm UMR 491, Université de la Méditerranée, 27 Bd J Moulin, 13385 Marseille Cedex 5, Inserm U751, Université de la Méditerranée, Marseille, Service de Neurophysiologie clinique, Hôpital de la Timone, Marseille, Laboratoire de Biologie Cellulaire, Hôpital de la Conception, Marseille, Service de Neurochirurgie fonctionnelle et Stéréotaxie, Hôpital de la Timone, Marseille, Service de Neurochirurgie, Hôpital de la Timone, Marseille

A two-step transcriptional analysis consisting of cDNA microarray experiments followed by quantitative RT-PCR validations was performed in the entorhinal cortex (epileptogenic area) of mesio-temporal lobe epilepsy patients (MTLE), as compared with lateral temporal neocortex (LTC) (non-epileptogenic control area) obtained from the same patients as well as to non-epileptic autopsic controls. Six genes consistently dysregulated were identified : three up-regulated genes encode proteins of the immune system : CD99, CD74, C3 ; two down-regulated genes encode neurotransmitter receptors (NPY1R, HTR2A) and a third one (FHL2) encodes a protein associating with the KCNE1 (mink) potassium channel subunit and with presenilin-2.Analysis of the qualitative and quantitative changes at the protein level, led to the confirmation of NPY1R downregulation and C3 upregulation by western blot and immunohistochemistry, respectively. Furthermore, immunohistochemistry experiments revealed the existence of perivascular infiltration of C3 positive leucocytes and/or detected C3 and membrane attack complexes on a subset of neurons within the EC of most MTLE patients tested.Overall, our data (published in Brain : Jamali et al., 2006) indicate that local dysregulation of the neurotransmission and complement system is a frequent event in human MTLE, and shed new insights on the molecular mechanisms that might contribute to the complex molecular bases of human drug-resistant mesial temporal lobe epilepsies.