Evaluation of a 5-HT Receptor Agonist in a Murine Model of Amyotrophic Lateral Sclerosis

Overview

Journal Sci Rep

Specialty Science

Date 2021 Dec 9

PMID 34880312

Citations 6

Authors

Alizee Arnoux

Estelle Ayme-Dietrich

Stephane Dieterle

Marc-Antoine Goy

Stephan Schann

Melanie Frauli

Laurent Monassier

Luc Dupuis

Affiliations

Soon will be listed here.

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-HT receptor (5-HTR) was upregulated in microglia of ALS mice. Its deletion worsened disease outcome in the Sod1 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-HTR agonist : BW723C86 (BW), in the Sod1 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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