Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis
Abstract Degeneration of brainstem serotonin neurons has been demonstrated in ALS patients and mouse models and was found responsible for the development of spasticity. Consistent with involvement of central serotonin pathways, 5-HT2B receptor (5-HT2BR) was upregulated in microglia of ALS mice. Its...
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Nature Portfolio
2021-12-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-02900-0 |
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author | Alizée Arnoux Estelle Ayme-Dietrich Stéphane Dieterle Marc-Antoine Goy Stephan Schann Mélanie Frauli Laurent Monassier Luc Dupuis |
author_facet | Alizée Arnoux Estelle Ayme-Dietrich Stéphane Dieterle Marc-Antoine Goy Stephan Schann Mélanie Frauli Laurent Monassier Luc Dupuis |
author_sort | Alizée Arnoux |
collection | DOAJ |
description | Abstract Degeneration of brainstem serotonin neurons has been demonstrated in ALS patients and mouse models and was found responsible for the development of spasticity. Consistent with involvement of central serotonin pathways, 5-HT2B receptor (5-HT2BR) was upregulated in microglia of ALS mice. Its deletion worsened disease outcome in the Sod1 G86R mouse model and led to microglial degeneration. In ALS patients, a polymorphism in HTR2B gene leading to higher receptor expression in CNS, was associated with increased survival in patients as well as prevention of microglial degeneration. Thus, the aim of our study was to determine the effect of a 5-HT2BR agonist : BW723C86 (BW), in the Sod1 G86R mouse model. Despite good pharmacokinetic and pharmacological profiles, BW did not ameliorate disease outcome or motor neuron degeneration in a fast progressing mouse model of ALS despite evidence of modulation of microglial gene expression. |
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language | English |
last_indexed | 2024-12-13T14:57:29Z |
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spelling | doaj.art-78eb463cf7e84a3299345d8d48c1867d2022-12-21T23:41:12ZengNature PortfolioScientific Reports2045-23222021-12-0111111110.1038/s41598-021-02900-0Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosisAlizée Arnoux0Estelle Ayme-Dietrich1Stéphane Dieterle2Marc-Antoine Goy3Stephan Schann4Mélanie Frauli5Laurent Monassier6Luc Dupuis7Mécanismes Centraux et Périphériques de la Neurodégénérescence, U1118, Inserm, UMR-S1118, CRBS, Université de StrasbourgLaboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, UR7296, Université de StrasbourgMécanismes Centraux et Périphériques de la Neurodégénérescence, U1118, Inserm, UMR-S1118, CRBS, Université de StrasbourgMécanismes Centraux et Périphériques de la Neurodégénérescence, U1118, Inserm, UMR-S1118, CRBS, Université de StrasbourgDomain TherapeuticsDomain TherapeuticsLaboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, UR7296, Université de StrasbourgMécanismes Centraux et Périphériques de la Neurodégénérescence, U1118, Inserm, UMR-S1118, CRBS, Université de StrasbourgAbstract Degeneration of brainstem serotonin neurons has been demonstrated in ALS patients and mouse models and was found responsible for the development of spasticity. Consistent with involvement of central serotonin pathways, 5-HT2B receptor (5-HT2BR) was upregulated in microglia of ALS mice. Its deletion worsened disease outcome in the Sod1 G86R mouse model and led to microglial degeneration. In ALS patients, a polymorphism in HTR2B gene leading to higher receptor expression in CNS, was associated with increased survival in patients as well as prevention of microglial degeneration. Thus, the aim of our study was to determine the effect of a 5-HT2BR agonist : BW723C86 (BW), in the Sod1 G86R mouse model. Despite good pharmacokinetic and pharmacological profiles, BW did not ameliorate disease outcome or motor neuron degeneration in a fast progressing mouse model of ALS despite evidence of modulation of microglial gene expression.https://doi.org/10.1038/s41598-021-02900-0 |
spellingShingle | Alizée Arnoux Estelle Ayme-Dietrich Stéphane Dieterle Marc-Antoine Goy Stephan Schann Mélanie Frauli Laurent Monassier Luc Dupuis Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis Scientific Reports |
title | Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis |
title_full | Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis |
title_fullStr | Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis |
title_full_unstemmed | Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis |
title_short | Evaluation of a 5-HT2B receptor agonist in a murine model of amyotrophic lateral sclerosis |
title_sort | evaluation of a 5 ht2b receptor agonist in a murine model of amyotrophic lateral sclerosis |
url | https://doi.org/10.1038/s41598-021-02900-0 |
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