Antidepressant Paroxetine Exerts Developmental Neurotoxicity in an iPSC-Derived 3D Human Brain Model

Xiali Zhong(Sun Yat-sen University), Georgina Harris(Johns Hopkins University), Lena Smirnova(Johns Hopkins University), Valentin Zufferey(University of Lausanne), Rita de Cássia da Silveira e Sá(Universidade Federal da Paraíba), Fabiele Baldino Russo(Universidade de São Paulo), Patrícia Braga(Universidade de São Paulo), Megan Chesnut(Johns Hopkins University), Marie‐Gabrielle Zurich(University of Lausanne), Helena T. Högberg(Johns Hopkins University), Thomas Härtung(University of Konstanz), David Pamies(Johns Hopkins University)
Frontiers in Cellular Neuroscience
February 21, 2020
10.3389/fncel.2020.00025
Cited by 80Open Access
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Abstract

testing battery to cover key events of brain development, could potentially overcome these challenges. In this study, we assess the DNT of paroxetine-a widely used SSRI which has shown contradictory evidence regarding effects on human brain development using a versatile, organotypic human induced pluripotent stem cell (iPSC)-derived brain model (BrainSpheres). At therapeutic blood concentrations, which lie between 20 and 60 ng/ml, Paroxetine led to an 80% decrease in the expression of synaptic markers, a 60% decrease in neurite outgrowth and a 40-75% decrease in the overall oligodendrocyte cell population, compared to controls. These results were consistently shown in two different iPSC lines and indicate that relevant therapeutic concentrations of Paroxetine induce brain cell development abnormalities which could lead to adverse effects.

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