References of "Van Den Ackerveken, Priscilla"
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See detailThe miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development
Van Den Ackerveken, Priscilla ULg; Mounier, Anaïs ULg; Huyghe, Aurélia et al

in Cell Death & Differentiation (in press)

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See detailPuzzling Out Synaptic Vesicle 2 Family Members Functions
Bartholomé, Odile ULg; Van Den Ackerveken, Priscilla ULg; Sanchez Gil, Judit ULg et al

in Frontiers in Molecular Neuroscience (2017)

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See detailThe miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development.
Van Den Ackerveken, Priscilla ULg; Mounier, Anaïs ULg; Huyghe, Aurelia et al

in Cell Death & Differentiation (2017)

MicroRNAs are important regulators of gene expression and are involved in cellular processes such as proliferation or differentiation, particularly during development of numerous organs including the ... [more ▼]

MicroRNAs are important regulators of gene expression and are involved in cellular processes such as proliferation or differentiation, particularly during development of numerous organs including the inner ear. However, it remains unknown if miRNAs are required during the earliest stages of otocyst and cochlear duct development. Here, we report that a conditional loss of Dicer expression in the otocyst impairs the early development of the inner ear as a result of the accumulation of DNA damage that trigger p53-mediated apoptosis. Moreover, cochlear progenitors in the prosensory domain do not exit the cell cycle. Our unbiased approach identified ItgA3 as a target of miR-183, which are both enriched in the otic vesicle. We observed that the repression of integrin alpha 3 by miR-183 controls cell proliferation in the developing cochlea. Collectively, our results reveal that Dicer and miRNAs play essential roles in the regulation of early inner ear development.Cell Death and Differentiation advance online publication, 4 August 2017; doi:10.1038/cdd.2017.127. [less ▲]

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See detailBehavioural phenotyping of SV2A lox/lox mice: Motor and anxiety-like features
Serrano Navacerrada, Maria Elisa ULg; Bartholomé, Odile ULg; Van Den Ackerveken, Priscilla ULg et al

Poster (2017)

Background: Epilepsy is one of the most common neurological disorders (Alexopoulos, 2004). Current anti-epileptic drugs, such as Levetiracetam (Keppra®) or Brivaracetam, mainly target the trans-membrane ... [more ▼]

Background: Epilepsy is one of the most common neurological disorders (Alexopoulos, 2004). Current anti-epileptic drugs, such as Levetiracetam (Keppra®) or Brivaracetam, mainly target the trans-membrane Synaptic Vesicle Protein 2A (Hamann et al., 2008). Studies on homozygous SV2A KO mice phenotype, prove the mice to suffer severe seizures and die within 3 weeks (Crowder et al., 1999), establishing a link between this protein and the epilepsy. In 2009, the availability of heterozygous SV2A (+/-) mice as research tool enabled shedding light on the role of protein SV2A, revealing no motor differences but anxiety-like features in these mice compared with the WT (Lamberty et al., 2009), and a pro-epileptic phenotype (Crowder et al., 1999; Kaminski et al., 2008). Recently, a floxed SV2A mouse model has been produced with the Cre/loxP recombination system, this model allows invalidating the protein in CA3 hippocampal region, not followed by epileptic seizures (Menten-Dedoyart et al., 2016). Objectives: Perform a first behavioural phenotyping of SV2A lox/lox mice. Methodology: Two experiments were conducted in parallel to evaluate the effect of 3 different genotypes in the phenotype: WT (Grik4-/-, SV2A lox/lox), HZ (Grik4 +/-, SV2A lox/+) and cKO (Grik4 +/-, SV2A lox/lox) in male (n = 42) and female (n = 33) separately . Mice were housed individually along the experiment, with standard food and water ad libitum. After an acclimatization period of 2 weeks, anxiety-like features as well as exploration abilities were evaluated in an elevated plus-maze (EPM) single session of 5 minutes). 3 days later, spontaneous locomotor activity and habituation to the environment were measured during 1 hour, 3 consecutive days, in the activity chambers (ACT). Results: One-way ANOVA in EPM data presented no significant differences between groups, either in males or in females. A significant difference was found, between time spent in close arms vs open arms (p<0.01; η2p = 0.738 males; η2p = 0.805 females). Mixed between-within subjects ANOVA in ACT reflected no significant differences between groups in both sexes, regarding spontaneous locomotor activity and acclimatization to the activity chamber (p>0.05). Statistical significant differences were found between the 3 days (p<0.01; η2p = 0.716 males; η2p = 0.663 females). Conclusion: Results indicate that a decrease in the hippocampal expresion of SV2A protein does not lead to major behavioral changes. Regarding locomotor activity, the results found in heterozygous SV2A (+/-) mice are in line with (Lamberty et al., 2009), however, our mice did not present anxiety-like features, being necessary a global decrease in brain SV2A levels and not only a partial loss in a restricted region of the brain. Further analyses increasing the number of mice per group, will allow us to intensify our power value from 50-60% (females-males) up to 80%, with large effect size and a signification of p<0.05. An additional test to evaluate the spatial memory may help us better understand the effect a specific reduction in SV2A hippocampal expression has on the phenotype of mice. [less ▲]

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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 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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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 detailOtotoxic drugs: difference in sensitivity between mice and guinea pigs.
Poirrier, Anne-Lise ULg; Van Den Ackerveken, Priscilla ULg; Kim, T. S. et al

in Toxicology Letters (2010), 193(1), 41-9

The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to ... [more ▼]

The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to develop an adult mouse model of ototoxic drug-induced hearing loss and to compare the ototoxicity in the adult mouse to that in the well-described guinea pig model. Mice are a powerful model organism, especially due to the large availability of antibodies, probes and genetic mutants. In this study, mice (n=114) and guinea pigs (n=35) underwent systemic treatment with either kanamycin or cisplatin. Auditory brainstem responses showed a significant threshold shift in guinea pigs 2 weeks after the beginning of the ototoxic treatment, while there was no significant hearing impairment recorded in mice. Hair cells and neuronal loss were correlated with hearing function in both guinea pigs and mice. These results indicate that the mouse is not a good model for ototoxicity, which should be taken into consideration in all further investigations concerning ototoxicity-induced hearing loss. [less ▲]

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See detailOxidative Stress in the Cochlea: An Update.
Poirrier, Anne-Lise ULg; Pincemail, Joël ULg; Van Den Ackerveken, Priscilla ULg et al

in Current Medicinal Chemistry (2010)

This paper will focus on understanding the role and action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the molecular and biochemical pathways responsible for the regulation of ... [more ▼]

This paper will focus on understanding the role and action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the molecular and biochemical pathways responsible for the regulation of the survival of hair cells and spiral ganglion neurons in the auditory portion of the inner ear. The pivotal role of ROS/RNS in ototoxicity makes them potentially valuable candidates for effective otoprotective strategies. In this review, we describe the major characteristics of ROS/RNS and the different oxidative processes observed during ototoxic cascades. At each step, we discuss their potential as therapeutic targets because an increasing number of compounds that modulate ROS/RNS processing or targets are being identified. [less ▲]

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