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- Title
Evaluation of a 5-HT<sub>2B</sub> receptor agonist in a murine model of amyotrophic lateral sclerosis.
- Authors
Arnoux, Alizée; Ayme-Dietrich, Estelle; Dieterle, Stéphane; Goy, Marc-Antoine; Schann, Stephan; Frauli, Mélanie; Monassier, Laurent; Dupuis, Luc
- 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 Sod1G86R 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 Sod1G86R 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.
- Subjects
MOTOR neuron diseases; AMYOTROPHIC lateral sclerosis; MICROGLIA; LABORATORY mice; OVERALL survival; NEURODEGENERATION; ANIMAL disease models
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-02900-0