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Effects of synchrotron-generated microbeams radiation on hippocampal architecture in epileptic mice

Objectifs

To observe the modifications of cellular organization in the hippocampus induced by synchrotron-generated microbeams radiation in a mouse model of epilepsy. This Master project is part of an ANR-funded project called “Synchrotron Therapy for Epilepsy” (STEP, coord. A. Depaulis).

Résumé

Synchrotron-generated microbeams radiation has emerged as an innovative radiosurgery procedure in neurology. It is based on the spatial segmentation of X-rays into low-divergent microbeams (50 μm) that are particularly safe to treat pathological brain regions, without tissular or behavioral side effects.
The present project aims at evaluating the use of this procedure as a new, non-invasive, therapy for epilepsy. Epilepsy is a neurological disorder characterized by spontaneous recurrent seizures. It affects up to 1% of the population among which 30% do not respond to antiepileptic drugs and resective surgery is the only option, when possible. Using a mouse model of focal, drug-resistant epilepsy, we are optimizing a synchrotron-generated microbeams radiation protocol to efficiently suppress seizures with minimal histological and behavioral side-effects. Using specific immunofluorescent antibodies and histochemistry, this Master’s project will examine the hypotheses that this treatment, (i) changes the microvasculature in the epileptogenic zone (hippocampus) and/or (ii) reduces the connectivity of the epileptic network. The Master student will learn to prepare brain slices from epileptic mice, to perform histolabeling for specific markers of microvasculature and microfilaments and to analyse the data with a slide scanner and confocal microscope and appropriate softwares.

Méthodes

Stereotaxic injection of kainic acid in mice and microsurgery procedures, Electroencephalography recordings, Magnetic Resonance Imaging (MRI), Cryostat brain sections, Immunofluorescence and histochemistry on brain slices, image acquisition (slide scanner, confocal microscope), Image analysis.

Références

Riban, V., Bouilleret, V., Pham-Lê, B. T., Fritschy, J.-M., Marescaux, C., & Depaulis, A. (2002). Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience, 112(1), 101‑111. https://doi.org/10.1016/s0306-4522(02)00064-7

Serduc, R., Bräuer-Krisch, E., Siegbahn, E. A., Bouchet, A., Pouyatos, B., Carron, R., Pannetier, N., Renaud, L., Berruyer, G., Nemoz, C., Brochard, T., Rémy, C., Barbier, E. L., Bravin, A., Le Duc, G., Depaulis, A., Estève, F., & Laissue, J. A. (2010). High-precision radiosurgical dose delivery by interlaced microbeam arrays of high-flux low-energy synchrotron X-rays. PloS One, 5(2), e9028. https://doi.org/10.1371/journal.pone.0009028

Studer, F., Jarre, G., Pouyatos, B., Nemoz, C., Brauer-Krisch, E., Muzelle, C., Serduc, R., Heinrich, C., & Depaulis, A. (2022). Aberrant neuronal connectivity in the cortex drives generation of seizures in rat absence epilepsy. Brain: A Journal of Neurology, awab438. https://doi.org/10.1093/brain/awab438

Domaines d'expertise requis

Neuroscience, Immunofluorescence, histochemistry, microscope analysis, statistical analysis

Contacts

Antoine Depaulis – DR1 Inserm
Email : Antoine.Depaulis@univ-grenoble-alpes.fr
Phone : 06 78 43 48 25

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GIN_offre-stage-M2_2022-2023_ADepaulis_20220707.pdf (PDF, 201053 Ko)

Mise à jour le 8 juillet 2022

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