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Corinne Collet - One of the best experts on this subject based on the ideXlab platform.
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Deletion of Serotonin 2B Receptor Provokes Structural Alterations of Mouse Dental Tissues
Calcified Tissue International, 2014Co-Authors: Sasha Dimitrova-nakov, Yassine Harichane, Arnaud Marchadier, Corinne Collet, Anne Baudry, Odile Kellermann, Michel GoldbergAbstract:Rampant caries and periodontal diseases occur in patients treated with antidepressants such as Serotonin reuptake inhibitors (SRIs; e.g., Prozac) which target the Serotonin transporter (SERT). As the Serotonin 2B Receptor (5HT_2BR) regulates SERT functionality and capacity to recognize SRIs, we investigated the potential role of 5HT_2BR on dental tissues by exploiting 5HT_2BR knockout (KO) mice. Compared to wild-type (WT) mice, several structural differences were identified in the teeth of KO mice. In the molar of KO mice, rod curvatures and twisting were altered compared to WT mice, suggesting involvement of 5HT_2BR at early stages of enamel formation. The volume of the KO enamel layer was also reduced, and larger porosities were observed in the prismatic enamel, with smaller crystallite thickness. Crystallite pattern disorganization and occlusal abrasion were enhanced in female KO mice, indicating a sexual dimorphism. In the incisor, no difference was detected in the width of the enamel layer between KO and WT mice; however, enamel maturation differed in absence of 5HT_2BR. Specifically, the outer aprismatic enamel border was 1.5- to 2-fold larger in KO compared to WT mice, together with a decreased etching pattern. Finally, although no noticeable difference was observed in dentin, the micro-CT three-dimensional pulp reconstruction evidenced a decrease in both length and width of dentin formation in the root canals of the KO versus WT mice. These data provide evidence that 5HT_2BR-mediated signaling pathways are involved in enamel formation and dentinogenesis.
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Serotonin 2B Receptor 5 ht2B r signals through prostacyclin and ppar s δ in osteoblasts
PLOS ONE, 2013Co-Authors: Jean-marie Launay, Luc Maroteaux, Yasmine Chabbiachengli, Marie Christine De Vernejoul, Corinne ColletAbstract:Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed that bone formation is reduced in the absence of the Serotonin Receptor 5-HT2B, causing impaired osteoblast proliferation, recruitment, and matrix mineralization. In this study, we investigated the signaling pathways responsible for the osteoblast defect in 5-HT2BR(-/-) mice. Notably, we investigated the phospholipase A2 pathway and synthesis of eicosanoids in 5-HT2BR(-/-) compared to wild type (WT) osteoblasts. Compared to control osteoblasts, the lack of 5-HT2B Receptors was only associated with a 10-fold over-production of prostacyclin (PGI2). Also, a specific prostacyclin synthase inhibitor (U51605) rescued totally osteoblast aggregation and matrix mineralization in the 5-HT2BR(-/-) osteoblasts without having any effect on WT osteoblasts. Prostacyclin is the endogenous ligand of the nuclear peroxisome proliferator activated Receptor s/δ (PPAR-s/δ), and its inhibition in 5-HT2BR(-/-) cells rescued totally the alkaline phosphatase and osteopontin mRNA levels, cell-cell adhesion, and matrix mineralization. We conclude that the absence of 5-HT2B Receptors leads to the overproduction of prostacyclin, inducing reduced osteoblast differentiation due to PPAR-s/δ -dependent target regulation and defective cell-cell adhesion and matrix mineralization. This study thus reveals a previously unrecognized cell autonomous osteoblast defect in the absence of 5-HT2BR and highlights a new pathway linking 5-HT2B Receptors and nuclear PPAR- s/δ via prostacyclin.
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Serotonin 2B Receptor (5-HT2B R) signals through prostacyclin and PPAR-ß/δ in osteoblasts.
PLoS ONE, 2013Co-Authors: Yasmine Chabbi-achengli, Jean-marie Launay, Luc Maroteaux, Marie Christine De Vernejoul, Corinne ColletAbstract:Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed that bone formation is reduced in the absence of the Serotonin Receptor 5-HT2B, causing impaired osteoblast proliferation, recruitment, and matrix mineralization. In this study, we investigated the signaling pathways responsible for the osteoblast defect in 5-HT2BR(-/-) mice. Notably, we investigated the phospholipase A2 pathway and synthesis of eicosanoids in 5-HT2BR(-/-) compared to wild type (WT) osteoblasts. Compared to control osteoblasts, the lack of 5-HT2B Receptors was only associated with a 10-fold over-production of prostacyclin (PGI2). Also, a specific prostacyclin synthase inhibitor (U51605) rescued totally osteoblast aggregation and matrix mineralization in the 5-HT2BR(-/-) osteoblasts without having any effect on WT osteoblasts. Prostacyclin is the endogenous ligand of the nuclear peroxisome proliferator activated Receptor s/δ (PPAR-s/δ), and its inhibition in 5-HT2BR(-/-) cells rescued totally the alkaline phosphatase and osteopontin mRNA levels, cell-cell adhesion, and matrix mineralization. We conclude that the absence of 5-HT2B Receptors leads to the overproduction of prostacyclin, inducing reduced osteoblast differentiation due to PPAR-s/δ -dependent target regulation and defective cell-cell adhesion and matrix mineralization. This study thus reveals a previously unrecognized cell autonomous osteoblast defect in the absence of 5-HT2BR and highlights a new pathway linking 5-HT2B Receptors and nuclear PPAR- s/δ via prostacyclin.
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Enamel alterations in Serotonin 2B Receptor knockout mice.
European Journal of Oral Sciences, 2011Co-Authors: Yassine Harichane, Sasha Dimitrova-nakov, Arnaud Marchadier, Corinne Collet, Anne Baudry, Catherine Vidal, Agnès Kamoun-goldrat, Odile Kellermann, Michel GoldbergAbstract:Harichane Y, Dimitrova-Nakov S, Marchadier A, Collet C, Baudry A, Vidal C, Kamoun-Goldrat A, Kellermann O, Goldberg M. Enamel alterations in Serotonin 2B Receptor knockout mice. Eur J Oral Sci 2011; 119 (Suppl. 1): 177–184. © 2011 Eur J Oral Sci The role of the Serotonin 2B Receptor (5-HT2BR) in enamel formation and mineralization was explored in adult 5HT2BR knockout (KO) mice compared with wild-type (WT) mice. In the molar, quantitative data obtained by micro-computed tomography imaging showed that the overall volume of the enamel layer was firmly reduced in KO mice. Defective mineralization was ascertained by energy-dispersive X-ray microanalysis. We also observed, using scanning electron microscopy, that parazones in the KO mice included two or three helicoidally twisted rods within Hunter–Schreger bands, instead of a single rod, as found in the WT mice. Minor disturbances were also detected in the incisors of KO mice. Structural modifications, thinner enamel crystallites, and porosities observed in KO mice indicate that the 5-HT2BR-mediated signaling pathways as part of the enamel formation process. These data provide a basis for evaluating the role of 5-HT2BR in ameloblast functions. Defects observed in the mineralization and structure of enamel in KO mice highlight that the 5-HT2BR interferes with the mechanisms directing amelogenesis.
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Enamel alterations in Serotonin 2B Receptor knockout mice.
European journal of oral sciences, 2011Co-Authors: Yassine Harichane, Sasha Dimitrova-nakov, Arnaud Marchadier, Corinne Collet, Anne Baudry, Catherine Vidal, Agnès Kamoun-goldrat, Odile Kellermann, Michel GoldbergAbstract:The role of the Serotonin 2B Receptor (5-HT(2B) R) in enamel formation and mineralization was explored in adult 5HT(2B) R knockout (KO) mice compared with wild-type (WT) mice. In the molar, quantitative data obtained by micro-computed tomography imaging showed that the overall volume of the enamel layer was firmly reduced in KO mice. Defective mineralization was ascertained by energy-dispersive X-ray microanalysis. We also observed, using scanning electron microscopy, that parazones in the KO mice included two or three helicoidally twisted rods within Hunter-Schreger bands, instead of a single rod, as found in the WT mice. Minor disturbances were also detected in the incisors of KO mice. Structural modifications, thinner enamel crystallites, and porosities observed in KO mice indicate that the 5-HT(2B) R-mediated signaling pathways as part of the enamel formation process. These data provide a basis for evaluating the role of 5-HT(2B) R in ameloblast functions. Defects observed in the mineralization and structure of enamel in KO mice highlight that the 5-HT(2B) R interferes with the mechanisms directing amelogenesis.
Luc Maroteaux - One of the best experts on this subject based on the ideXlab platform.
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A positive association between a polymorphism in the HTR2B gene and cocaine-crack in a French Afro-Caribbean population
The World Journal of Biological Psychiatry, 2019Co-Authors: Jérôme Lacoste, S. Lamy, Nicolas Ramoz, Nicolas Ballon, Louis Jehel, Luc Maroteaux, Florence ThibautAbstract:Objectives: Cocaine dependence has a strong heritability component. The aim of this study was to investigate the putative association between the Serotonin 2B Receptor gene (HTR2B), crack use disor...
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A positive association between a polymorphism in the HTR2B gene and cocaine-crack in a French Caribbean population
World Journal of Biological Psychiatry, 2019Co-Authors: Jérôme Lacoste, S. Lamy, Nicolas Ramoz, Nicolas Ballon, Louis Jehel, Luc Maroteaux, Florence ThibautAbstract:Objectives : Cocaine dependence has a strong heritability component. The aim of this study was to investigate the putative association between the Serotonin 2B Receptor gene (HTR2B), crack use disorders and impulsivity. Methods : A French Caribbean male population of patients with crack use disorders (n=80) w as compared to healthy male controls (n=60). Comorbid ADHD and impulsivity were assessed. Five Single Nucleotide Polymorphisms (SNPs) in the HTR2B gene on chromosome 2 were selected: rs643700, rs 6736017, rs1549339, rs17586428 and rs3806545 Thes e five SNPs were chosen to cover most of the linkage disequilibrium (LD) blocks in HTR2B. The French translation of the Baratt Impulsivity Scale BIS -11 was used to evaluate impulsivity. Comorbid ADHD was diagnosed using the Wender Utah Rating Scale-25 item for the Attention Deficit-Hyperactivity Disorder. Results : We have found a positive association between the rs6736017 polymorphism and crack use disorders in a French Afro-caribbean male population. Conclusion : The risk effect of HTR2B rs6736017 appeare d to be specific to individuals who are crack users rather than being driven by impulsivity alone or ADHD alone
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A positive association between a polymorphism in the HTR2B gene and cocaine-crack in a French Afro-Caribbean population
2019Co-Authors: Jérôme Lacoste, S. Lamy, Nicolas Ramoz, Nicolas Ballon, Louis Jehel, Luc Maroteaux, Florence ThibautAbstract:Objectives: Cocaine dependence has a strong heritability component. The aim of this study was to investigate the putative association between the Serotonin 2B Receptor gene (HTR2B), crack use disorders and impulsivity. Methods: A French Afro-Caribbean male population of patients with crack use disorders (n = 80) was compared to healthy Afro-Caribbean male controls (n = 60). Comorbid ADHD and impulsivity were assessed. Five single nucleotide polymorphisms (SNPs) in the HTR2B gene were selected: rs643700, rs6736017, rs1549339, rs17586428 and rs3806545. These SNPs were chosen to include most of the linkage disequilibrium blocks in the HTR2B gene. The French translation of the Barratt Impulsivity Scale BIS-11 was used to evaluate impulsivity. Comorbid ADHD was diagnosed using the Wender Utah Rating Scale-25 item for Attention Deficit-Hyperactivity Disorder. Results: We have observed a positive association between the rs6736017 polymorphism and crack use disorders in a French Afro-Caribbean male population. Conclusions: In our population, the risk effect of HTR2B rs6736017 appeared to be specific to individuals with crack use disorders rather than being driven by impulsivity or ADHD alone.
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Translational studies support a role for Serotonin 2B Receptor (HTR2B) gene in aggression-related cannabis response
Molecular Psychiatry, 2018Co-Authors: Janitza L. Montalvo-ortiz, Luc Maroteaux, Hang Zhou, Ivana D’andrea, Adriana Lori, Alicia Smith, Kerry J. Ressler, Yaira Z. Nuñez, Lindsay A. Farrer, Hongyu ZhaoAbstract:Cannabis use is increasing in the United States, as are its adverse effects. We investigated the genetics of an adverse consequence of cannabis use: cannabis-related aggression (CRA) using a genome-wide association study (GWAS) design. Our GWAS sample included 3269 African Americans (AAs) and 2546 European Americans (EAs). An additional 89 AA subjects from the Grady Trauma Project (GTP) were also examined using a proxy-phenotype replication approach. We identified genome-wide significant risk loci contributing to CRA in AAs at the Serotonin Receptor 2B Receptor gene ( HTR2B ), and the lead SNP, HTR2B* rs17440378, showed nominal association to aggression in the GTP cohort of cannabis-exposed subjects. A priori evidence linked HTR2B to impulsivity/aggression but not to cannabis response. Human functional data regarding the HTR2B variant further supported our finding. Treating an Htr2B ^−/− knockout mouse with THC resulted in increased aggressive behavior, whereas wild-type mice following THC administration showed decreased aggression in the resident-intruder paradigm, demonstrating that HTR2B variation moderates the effects of cannabis on aggression. These concordant findings in mice and humans implicate HTR2B as a major locus associated with cannabis-induced aggression.
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Mice lacking the Serotonin 5-HT2B Receptor as an animal model of resistance to selective Serotonin reuptake inhibitors antidepressants.
European Neuropsychopharmacology, 2016Co-Authors: Silvina L Diaz, Nicolas Narboux-nême, Katia Boutourlinsky, Stéphane Doly, Luc MaroteauxAbstract:Depressive disorders are among the most prevalent neuropsychiatric dysfunctions worldwide, with high rates of resistance to antidepressant treatment. Genetic factors clearly contribute to the manifestation of depression as well as to the response to antidepressants. Transgenic mouse models appear as seminal tools to disentangle this complex disorder. Here, we analyzed new key aspects of the phenotype of knock-out mice for the gene encoding the Serotonin 2B Receptor (Htr(2B)(-/-)), including basal phenotype, ability to develop a depressive-like phenotype upon chronic isolation, and effect of chronic exposure to fluoxetine on chronically stressed Htr(2B)(-/-) mice. We find, here, that Htr(2B)(-/-) mice display an antidepressant-like phenotype, which includes reduced latency to feed in the novelty suppressed feeding test, basal increase in hippocampal BDNF levels, no change in TrkB and p75 protein levels, and an increased preference for sucrose consumption compared to wild type (Htr(2B)(+/+)) mice. Nevertheless, we show that these mice can develop depressive-like behaviors when socially isolated during four weeks. Selective Serotonin reuptake inhibitors (SSRI) have been previously shown to be ineffective in non-stressed Htr(2B)(-/-) mice. We evaluated, here, the effects of the SSRI fluoxetine in chronically stressed Htr(2B)(-/-) mice and similarly no behavioral or plastic effect was induced by this antidepressant. All together, these results highlight the suitability to study resistance to SSRI antidepressants of this mouse model displaying panoply of conditions among which behavioral, neurotrophic and plastic causative factors can be analyzed.
Barbara F Hales - One of the best experts on this subject based on the ideXlab platform.
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In utero exposure to venlafaxine, a Serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart Serotonin signaling in the rat.
Birth Defects Research Part A: Clinical and Molecular Teratology, 2016Co-Authors: Laetitia Laurent, Chunwei Huang, Sheila R Ernest, Anick Berard, Cathy Vaillancourt, Barbara F HalesAbstract:Human studies are inconsistent with respect to an association between treatment with selective Serotonin and Serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart Serotonin signaling in the rat. Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the Serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the Serotonin 2B Receptor (5-HT2B /Htr2B) and of fibroblast growth factor 8 was induced in fetal hearts. In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in Serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.
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In utero exposure to venlafaxine, a Serotonin–norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart Serotonin signaling in the rat
Birth Defects Research Part A: Clinical and Molecular Teratology, 2016Co-Authors: Laetitia Laurent, Chunwei Huang, Sheila R Ernest, Anick Berard, Cathy Vaillancourt, Barbara F HalesAbstract:Background Human studies are inconsistent with respect to an association between treatment with selective Serotonin and Serotonin–norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart Serotonin signaling in the rat. Methods Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Results Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the Serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the Serotonin 2B Receptor (5-HT2B/Htr2B) and of fibroblast growth factor 8 was induced in fetal hearts. Conclusion In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in Serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044–1055, 2016. © 2016 Wiley Periodicals, Inc.
Michel Goldberg - One of the best experts on this subject based on the ideXlab platform.
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Comparative studies between mice molars and incisors are required to draw an overview of enamel structural complexity
Frontiers in Physiology, 2014Co-Authors: Michel Goldberg, Yassine Harichane, Sasha Dimitrova-nakov, Odile Kellermann, Anne BaudryAbstract:In the field of dentistry, the murine incisor has long been considered as an outstanding model to study amelogenesis. However, it clearly appears that enamel from wild type mouse incisors and molars presents several structural differences. In incisor, exclusively radial enamel is observed. In molars, enamel displays a high level of complexity since the inner part is lamellar whereas the outer enamel shows radial and tangential structures. Recently, the Serotonin 2B Receptor (5-HT2BR) was shown to be involved in ameloblast function and enamel mineralization. The incisors from 5HT2BR knockout (KO) mice exhibit mineralization defects mostly in the outer maturation zone and porous matrix network in the inner zone. In the molars, the mutation affects both secretory and maturation stages of amelogenesis since pronounced alterations concern overall enamel structures. Molars from 5HT2BR KO mice display reduction in enamel thickness, alterations of inner enamel architecture including defects in Hunter-Schreger Bands arrangements, and altered maturation of the outer radial enamel. Differences of enamel structure were also observed between incisor and molar from other KO mice depleted for genes encoding enamel extracellular matrix proteins.
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Deletion of Serotonin 2B Receptor Provokes Structural Alterations of Mouse Dental Tissues
Calcified Tissue International, 2014Co-Authors: Sasha Dimitrova-nakov, Yassine Harichane, Arnaud Marchadier, Corinne Collet, Anne Baudry, Odile Kellermann, Michel GoldbergAbstract:Rampant caries and periodontal diseases occur in patients treated with antidepressants such as Serotonin reuptake inhibitors (SRIs; e.g., Prozac) which target the Serotonin transporter (SERT). As the Serotonin 2B Receptor (5HT_2BR) regulates SERT functionality and capacity to recognize SRIs, we investigated the potential role of 5HT_2BR on dental tissues by exploiting 5HT_2BR knockout (KO) mice. Compared to wild-type (WT) mice, several structural differences were identified in the teeth of KO mice. In the molar of KO mice, rod curvatures and twisting were altered compared to WT mice, suggesting involvement of 5HT_2BR at early stages of enamel formation. The volume of the KO enamel layer was also reduced, and larger porosities were observed in the prismatic enamel, with smaller crystallite thickness. Crystallite pattern disorganization and occlusal abrasion were enhanced in female KO mice, indicating a sexual dimorphism. In the incisor, no difference was detected in the width of the enamel layer between KO and WT mice; however, enamel maturation differed in absence of 5HT_2BR. Specifically, the outer aprismatic enamel border was 1.5- to 2-fold larger in KO compared to WT mice, together with a decreased etching pattern. Finally, although no noticeable difference was observed in dentin, the micro-CT three-dimensional pulp reconstruction evidenced a decrease in both length and width of dentin formation in the root canals of the KO versus WT mice. These data provide evidence that 5HT_2BR-mediated signaling pathways are involved in enamel formation and dentinogenesis.
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Enamel alterations in Serotonin 2B Receptor knockout mice.
European Journal of Oral Sciences, 2011Co-Authors: Yassine Harichane, Sasha Dimitrova-nakov, Arnaud Marchadier, Corinne Collet, Anne Baudry, Catherine Vidal, Agnès Kamoun-goldrat, Odile Kellermann, Michel GoldbergAbstract:Harichane Y, Dimitrova-Nakov S, Marchadier A, Collet C, Baudry A, Vidal C, Kamoun-Goldrat A, Kellermann O, Goldberg M. Enamel alterations in Serotonin 2B Receptor knockout mice. Eur J Oral Sci 2011; 119 (Suppl. 1): 177–184. © 2011 Eur J Oral Sci The role of the Serotonin 2B Receptor (5-HT2BR) in enamel formation and mineralization was explored in adult 5HT2BR knockout (KO) mice compared with wild-type (WT) mice. In the molar, quantitative data obtained by micro-computed tomography imaging showed that the overall volume of the enamel layer was firmly reduced in KO mice. Defective mineralization was ascertained by energy-dispersive X-ray microanalysis. We also observed, using scanning electron microscopy, that parazones in the KO mice included two or three helicoidally twisted rods within Hunter–Schreger bands, instead of a single rod, as found in the WT mice. Minor disturbances were also detected in the incisors of KO mice. Structural modifications, thinner enamel crystallites, and porosities observed in KO mice indicate that the 5-HT2BR-mediated signaling pathways as part of the enamel formation process. These data provide a basis for evaluating the role of 5-HT2BR in ameloblast functions. Defects observed in the mineralization and structure of enamel in KO mice highlight that the 5-HT2BR interferes with the mechanisms directing amelogenesis.
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Enamel alterations in Serotonin 2B Receptor knockout mice.
European journal of oral sciences, 2011Co-Authors: Yassine Harichane, Sasha Dimitrova-nakov, Arnaud Marchadier, Corinne Collet, Anne Baudry, Catherine Vidal, Agnès Kamoun-goldrat, Odile Kellermann, Michel GoldbergAbstract:The role of the Serotonin 2B Receptor (5-HT(2B) R) in enamel formation and mineralization was explored in adult 5HT(2B) R knockout (KO) mice compared with wild-type (WT) mice. In the molar, quantitative data obtained by micro-computed tomography imaging showed that the overall volume of the enamel layer was firmly reduced in KO mice. Defective mineralization was ascertained by energy-dispersive X-ray microanalysis. We also observed, using scanning electron microscopy, that parazones in the KO mice included two or three helicoidally twisted rods within Hunter-Schreger bands, instead of a single rod, as found in the WT mice. Minor disturbances were also detected in the incisors of KO mice. Structural modifications, thinner enamel crystallites, and porosities observed in KO mice indicate that the 5-HT(2B) R-mediated signaling pathways as part of the enamel formation process. These data provide a basis for evaluating the role of 5-HT(2B) R in ameloblast functions. Defects observed in the mineralization and structure of enamel in KO mice highlight that the 5-HT(2B) R interferes with the mechanisms directing amelogenesis.
Laetitia Laurent - One of the best experts on this subject based on the ideXlab platform.
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In utero exposure to venlafaxine, a Serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart Serotonin signaling in the rat.
Birth Defects Research Part A: Clinical and Molecular Teratology, 2016Co-Authors: Laetitia Laurent, Chunwei Huang, Sheila R Ernest, Anick Berard, Cathy Vaillancourt, Barbara F HalesAbstract:Human studies are inconsistent with respect to an association between treatment with selective Serotonin and Serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart Serotonin signaling in the rat. Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the Serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the Serotonin 2B Receptor (5-HT2B /Htr2B) and of fibroblast growth factor 8 was induced in fetal hearts. In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in Serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.
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In utero exposure to venlafaxine, a Serotonin–norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart Serotonin signaling in the rat
Birth Defects Research Part A: Clinical and Molecular Teratology, 2016Co-Authors: Laetitia Laurent, Chunwei Huang, Sheila R Ernest, Anick Berard, Cathy Vaillancourt, Barbara F HalesAbstract:Background Human studies are inconsistent with respect to an association between treatment with selective Serotonin and Serotonin–norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart Serotonin signaling in the rat. Methods Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Results Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the Serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the Serotonin 2B Receptor (5-HT2B/Htr2B) and of fibroblast growth factor 8 was induced in fetal hearts. Conclusion In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in Serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044–1055, 2016. © 2016 Wiley Periodicals, Inc.
