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See detailStudy of the SV2A protein role in Epilepsy.
Bartholomé, Odile ULg; Van Den Ackerveken, Priscilla ULg; Wislet, Sabine ULg et al

Poster (2016, October)

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See detailDevelopment and validation of a new mouse model to investigate the role of sv2a in epilepsy
MENTEN, Catherine ULg; Serrano Navacerrada, Maria Elisa ULg; Bartholomé, Odile ULg et al

in PLoS ONE (2016)

SV2A is a glycoprotein present in the membranes of most synaptic vesicles. Although it has been highly conserved throughout evolution, its physiological role remains largely unknown. Nevertheless ... [more ▼]

SV2A is a glycoprotein present in the membranes of most synaptic vesicles. Although it has been highly conserved throughout evolution, its physiological role remains largely unknown. Nevertheless, Levetiracetam, a very effective anti-epileptic drug, has been recently demonstrated to bind to SV2A. At present, our understanding of the normal function of SV2A and its possible involvement in diseases like epilepsy is limited. With this study, we sought to develop a relevant model enabling analysis of SV2A's role in the occurrence or progression of epilepsy. For this purpose, we generated a floxed SV2A mouse model with conditional alleles carrying LoxP sites around exon 3 by means of a gene-targeting strategy. The SV2A lox/lox mouse line is indistinguishable from wild-type mice. When the recombination was observed in all cells, a model of mice with both SV2A alleles floxed around exon 3 recapitulated the phenotype of SV2A KO mice, including seizures. However, the specific invalidation of SV2A in the CA3 hippocampal region was not followed by epileptic seizures or decrease in the epileptic threshold on pentylenetetrazol (PTZ) test. These results demonstrate that the floxed SV2A mouse line has been successfully established. This transgenic mouse model will be useful for investigating SV2A functions related to cell types and developmental stages. [less ▲]

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See detailMicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5.
Huyghe, Aurelia; Van Den Ackerveken, Priscilla ULg; SACHELI, Rosalie ULg et al

in Cell Reports (2015), 13

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the ... [more ▼]

The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the specification of these progenitors remain elusive. In the present study, by combining microarray analyses with conditional deletion of Dicer in the developing inner ear, we identified that miR-124 controls cell fate in the developing organ of Corti. By targeting secreted frizzled-related protein 4 (Sfrp4) and Sfrp5, two inhibitors of the Wnt pathway, we showed that miR-124 controls the β-catenin-dependent and also the PCP-related non-canonical Wnt pathways that contribute to HC differentiation and polarization in the organ of Corti. Thus, our work emphasizes the importance of miR-124 as an epigenetic safeguard that fine-tunes the expression of genes critical for cell patterning during cochlear differentiation. [less ▲]

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See detailGene transfer in inner ear cells: a challenging race
Sacheli, Rosalie ULg; Delacroix, Laurence ULg; Van Den Ackerveken, Priscilla ULg et al

in Gene Therapy (2013), 20

Recent advances in human genomics led to the identification of numerous defective genes causing deafness, which represent novel putative therapeutic targets. Future gene-based treatment of deafness ... [more ▼]

Recent advances in human genomics led to the identification of numerous defective genes causing deafness, which represent novel putative therapeutic targets. Future gene-based treatment of deafness resulting from genetic or acquired sensorineural hearing loss may include strategies ranging from gene therapy to antisense delivery. For successful development of gene therapies, a minimal requirement involves the engineering of appropriate gene carrier systems. Transfer of exogenous genetic material into the mammalian inner ear using viral or non-viral vectors has been characterized over the last decade. The nature of inner ear cells targeted, as well as the transgene expression level and duration, are highly dependent on the vector type, the route of administration and the strength of the promoter driving expression. This review summarizes and discusses recent advances in inner ear gene-transfer technologies aimed at examining gene function or identifying new treatment for inner ear disorders. [less ▲]

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See detailIn vivo protection of spiral ganglion neurons by bryostatin 1: preliminary results
POIRRIER, Anne-Lise ULg; Van Den Ackerveken, Priscilla ULg; Defourny, Jean et al

in Advances in Cellular and Molecular Otolaryngology (2013), 1

Background: We aim to demonstrate the effect of bryostatin 1, a macrocyclic lactone that activates protein kinase C, on spiral ganglion neurons (SGNs) of adult guinea pigs deafened by aminoglycoside ... [more ▼]

Background: We aim to demonstrate the effect of bryostatin 1, a macrocyclic lactone that activates protein kinase C, on spiral ganglion neurons (SGNs) of adult guinea pigs deafened by aminoglycoside. Methodology: Twenty-one guinea pigs were deafened by the aminoglycoside gentamicin and then treated by continuous infusion of experimental molecule for 1 month. The experimental molecule was bryostatin 1, artificial perilymph (negative control), or neurotrophins and an apoptosis inhibitor (positive control). Neuronal density in the spiral ganglia was quantified. Results: Bryostatin 1 protected SGNs after a gentamicin challenge. Conclusions: Bryostatin 1 has a neuroprotective effect when administered continuously at low doses in adult guinea pigs. [less ▲]

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