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

Poster (2016, October)

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See detailEVALUATION OF SV2Alox/Cre TRANSGENIC MICE USING [18F]UCB-H IN VITRO AUTORADIOGRAPHY
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; MENTEN, Catherine ULiege et al

Poster (2016, March 09)

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to study in vivo SV2A brain proteins [3, 4]. The present pilot study was undertaken to evaluate for the first time in vivo in rats SV2A expression in the Kaïnic Acid (KA) epilepsy model [5]. Although this model is well studied in mice, few reports were devoted to rats. Imaging-wise, rats are very interesting thanks to a bigger brain size (reduction of the partial volume effect). Methods Three male Sprague-Dawley were used, one injected with saline and two with multiple KA injections (3 x 5mg/kg) [6]. 75 days later, when spontaneous seizures started to appear, microPET (Focus 120 ) was performed under isoflurane anesthesia (2.5-3 % in air) for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) followed by MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed as SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results obtained in KA treated rats showed that [18F]UCB-H was able to detect important modifications for SV2A in relevant regions for epilepsy and appears as a valuable tool to follow in vivo SV2A through longitudinal studies. KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [less ▲]

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See detailDevelopment and validation of a new mouse model to investigate the role of sv2a in epilepsy
MENTEN, Catherine ULiege; Serrano Navacerrada, Maria Elisa ULiege; Bartholomé, Odile ULiege 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 detailEVALUATION OF SV2Alox/Cre TRANSGENIC MOUSE USING [18F]UCB-H IN IN VITRO AUTORADIOGRAPHY
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; MENTEN, Catherine ULiege et al

Poster (2015, September 04)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking. Interestingly, the SV2A has been identify as the binding site for ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking. Interestingly, the SV2A has been identify as the binding site for the antiepileptic drug levetiracetam, showing a close relation between the epilepsy, the dysregulation of the SV2A levels and the response to antiepileptic medications. SV2A floxed-mice were developed using a cre-lox technique, leading to a strong decrease of SV2A expression in the CA3 field of the hippocampus. We aim here to validate this model using [18F]UCB-H, a novel PET imaging radiotracer with a nanomolar affinity for human SV2A. Methods: In vitro autoradiography were performed on SV2Alox/Cre+ transgenic mouse brain slices. SV2Alox/Cre- mouse was used as control. To obtain a structural reference, brain slices underwent eosin-haematoxylin staining. Images of both procedures were coregistered using π-PMOD software. Regions of interest (Dentate Gyrus, CA1, CA2 and CA3) were drawn according to a stereotaxic atlas of the mouse brain. Results: Analyses showed significant differences in radiotracer binding (p<0.001) between SV2Alox/Cre+ mouse and SV2Alox/Cre- mouse highlighting an important reduction for the labelling density in Ammon's horn, particularly in CA1, compared to Dentate Gyrus where the diminution was less marked. Conclusions: Here, we used the radiotracer [18F]UCB-H to probe the decreased expression of SV2A protein in the hippocampus of SV2Alox/Cre+ mouse versus SV2Alox/Cre- control mouse. Our results contribute to the validation of the model, and encourage us to proceed with further longitudinal and behavioural studies. [less ▲]

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See detailPrevention of murine sclerodermatous chronic graft-versus-host disease by Rapamycin
Belle, Ludovic ULiege; BINSFELD, Marilène ULiege; DUBOIS, Sophie ULiege et al

in Biology of Blood & Marrow Transplantation (2013, February), 19

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See detailPrevention of murine sclerodermatous chronic graft-versus-host disease by Rapamycin
Belle, Ludovic ULiege; Binsfeld, Marilène ULiege; Dubois, Sophie et al

Poster (2013)

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See detailRapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice
Belle, Ludovic ULiege; BINSFELD, Marilène ULiege; Dubois, Sophie et al

in Bone Marrow Transplantation (2012, April), 47 Suppl 1

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See detailWhat is the Contribution of Host-Derived CMV Immunity after Allogeneic Transplantation following Non-Myeloablative Conditioning?
MENTEN, Catherine ULiege; Castermans, E.; Hannon, Muriel ULiege et al

in Haematologica (2012), 97(Supplement 1), 720

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See detailEvidence for Expansion of Host-derived CMV-specific CD8+ T cells after Allogeneic Transplantation with Non-Myeloablative Conditioning
MENTEN, Catherine ULiege; Castermans, E.; Hannon, Muriel ULiege et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 16

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See detailRapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice
Belle, Ludovic ULiege; Binsfeld, Marilène ULiege; DUBOIS, Sophie ULiege et al

Conference (2012)

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that ... [more ▼]

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bone marrow cells and 70x106 splenocytes from B10.D2 donor mice. Twenty-one days later, all mice developed cGvHD. For the severe model, donor B10.D2 mice were injected with 0.5x106 splenocytes from Balb/C twenty-one days before transplantation. All mice from the severe model (n=8) died a median of 32 days while 3 of 7 mice in the classical model survived beyond day 52. Mean survival was decreased in the severe model compared to the classical model (32 days versus 37 days; p=0.0185). Recipient mice in the severe group experienced higher weight loss, hair loss and skin fi brosis. Numbers of T lymphocytes (231.9 ± 151.4 versus 951 ± 532.8; p=0.0032) and CD4+ T cells (63.25 ± 41.93 versus 135.0 ± 14.39; p=0.0018) per microliter of blood at day 21 were lower in the severe group than in the classical model. Moreover, number of regulatory T cells (Tregs) was decreased in the severe model (1.250 ± 0.8864 versus 8.000 ± 6.753; p=0.0151). We then investigated whether rapamycin administration could prevent GVHD in the severe model. All (n=8) mice treated with PBS (placebo) died a median of 32 days after transplantation, while 6 of 8 mice given 1 mg/kg/day i.p. rapamycin survived beyond day 52 (p=0.0012). Number of Tregs/μl was higher at day 21 in rapamycin-treated mice than in mice given PBS (2.000±1.195 versus 1.250±0.8864; p=0.0796). Moreover, number of naïve CD4+T (10.00±4.192 versus 30.25±5.185; p= 0.0089) and effector memory T cells (EMT) (30.67±3.180 versus 67.33±7.881; p= 0.0125) were higher in rapamycin mice. Finally, proliferation of EMT (assessed by fl ow cytometry using Ki-67) was higher in PBS than in rapamycin mice (45.28%±4.084 versus 31.90%± 2.003; p=0.0474). Conclusion: We have developed a mice model of severe cGVHD. Interestingly, rapamycin prevented death from cGVHD in that model, perhaps through in vivo expansion of Treg. [less ▲]

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See detailKinetic study of the antibody response during the blood meal of Ixodes ricinus: Implication on plasma cell maturation in vivo and for anti-Ixodes vaccination
MENTEN, Catherine ULiege; couvreur, B.; Jolois, Olivier ULiege et al

in Vaccine (2011)

Anti-tick vaccination could be an ideal solution to prevent pathogen transmission, but none is currently available against Ixodes ticks. Recently, we showed that adult Ixodes ricinus infestation on mice ... [more ▼]

Anti-tick vaccination could be an ideal solution to prevent pathogen transmission, but none is currently available against Ixodes ticks. Recently, we showed that adult Ixodes ricinus infestation on mice decreases the specific antibody production to BSA injected during infestation. Here, a kinetic study of seric levels of BSA-specific antibodies was performed to evaluate the B memory cell differentiation in Balb/c mice and the capacity of specific B memory cells to respond to BSA during infestation. We concluded that the tick blood meal inhibits or impairs the local differentiation of mature B cells into plasma cells, but does not alter the formation of memory B cell. Accordingly, this mechanism should not be an impediment to anti-Ixodes vaccination. [less ▲]

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