Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers Inc.
Résumé : International audience
An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the 'latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury. © 2016 IEEE.
38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2016
Unknown, Unknown or Invalid Region

hal-01467552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467552
DOI : 10.1109/EMBC.2016.7591605

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Childhood absence epilepsy is a prototypic form of generalized nonconvulsive epilepsy characterized by short impairments of consciousness concomitant with synchronous and bilateral spike-and-wave discharges in the electroencephalogram. For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a genetic selection, constitute an original mouse model "in mirror" of absence epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the discovery of potential biomarkers is increasingly recognized. Interestingly, statistical analysis tools specifically adapted to IMS data sets and methods for the identification of detected proteins play an essential role. In this study, a new cross-classification comparative design using a combined discrete wavelet transformation-support vector machine classification was developed to discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z ratios were thus highlighted as potential markers with very high recognition rates (87-99%). Seven of these potential markers were identified using a top-down approach, in particular a fragment of Synapsin-I. This protein is yet suspected to be involved in epilepsy. Immunohistochemistry and Western Blot experiments confirmed the differential expression of Synapsin-I observed by IMS, thus tending to validate our approach. Functional assays are being performed to confirm the involvement of Synapsin-I in the mechanisms underlying childhood absence epilepsy.
ISSN: 1535-3893

hal-00877728
https://hal.archives-ouvertes.fr/hal-00877728
DOI : 10.1021/pr3006974
PUBMED : 22994238

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
ISSN: 1061-4036

hal-01544763
https://hal.archives-ouvertes.fr/hal-01544763
DOI : 10.1038/ng.2601

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
UNLABELLED: Glioblastoma (GB) is the most frequent and aggressive tumor of the central nervous system. There is currently growing interest in proteomic studies of GB, particularly with the aim of identifying new prognostic or therapeutic response markers. However, comparisons between different proteomic analyses of GB have revealed few common differentiated proteins. The types of control samples used to identify such proteins may in part explain the different results obtained. We therefore tried to determine which control samples would be most suitable for GB proteomic studies. We used an isotope-coded protein labeling (ICPL) method followed by mass spectrometry to reveal and compare the protein patterns of two commonly used types of control sample: GB peritumoral brain zone samples (PBZ) from six patients and epilepsy surgery brain samples (EB) pooled from three patients. The data obtained were processed using AMEN software for network analysis. We identified 197 non-redundant proteins and 35 of them were differentially expressed. Among these 35 differentially expressed proteins, six were over-expressed in PBZ and 29 in EB, showing different proteomic patterns between the two samples. Surprisingly, EB appeared to display a tumoral-like expression pattern in comparison to PBZ. In our opinion, PBZ may be more appropriate control sample for GB proteomic analysis. BIOLOGICAL SIGNIFICANCE: This manuscript describes an original study in which we used an isotope-coded protein labeling method followed by mass spectrometry to identify and compare the protein patterns in two types of sample commonly used as control for glioblastoma (GB) proteomic analysis: peritumoral brain zone and brain samples obtained during surgery for epilepsy. The choice of control samples is critical for identifying new prognostic and/or diagnostic markers in GB.
ISSN: 1874-3919

inserm-00871494
http://www.hal.inserm.fr/inserm-00871494
http://www.hal.inserm.fr/inserm-00871494/document
http://www.hal.inserm.fr/inserm-00871494/file/ManuscritProt-accepted.pdf
DOI : 10.1016/j.jprot.2013.04.031