TY - JOUR
KW - ADHD
KW - Animals
KW - Antidepressive Agents
KW - Autism Spectrum Disorder
KW - Autism Spectrum Disorder
KW - Autistic Disorder
KW - Brain
KW - Female
KW - HiPSC
KW - Humans
KW - Infant, Newborn
KW - Leukoencephalopathies
KW - Major depressive disorders
KW - organoids
KW - Pregnancy
KW - Selective Serotonin Reuptake Inhibitors
KW - Single-cell analyses
KW - Transcriptome
AU - Luciana Simões Rafagnin Marinho
AU - Gabrielly Maria Denadai Chiarantin
AU - Juliane Midori Ikebara
AU - Débora Sterzeck Cardoso
AU - Théo Henrique de Lima-Vasconcellos
AU - Guilherme Shigueto Vilar Higa
AU - Mariana Sacrini Ayres Ferraz
AU - Roberto De Pasquale
AU - Silvia Honda Takada
AU - Fabio Papes
AU - Alysson R. Muotri
AU - Alexandre Hiroaki Kihara
AB - The use of antidepressants during pregnancy benefits the mother's well-being, but the effects of such substances on neurodevelopment remain poorly understood. Moreover, the consequences of early exposure to antidepressants may not be immediately apparent at birth. In utero exposure to selective serotonin reuptake inhibitors (SSRIs) has been related to developmental abnormalities, including a reduced white matter volume. Several reports have observed an increased incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) after prenatal exposure to SSRIs such as sertraline, the most widely prescribed SSRI. The advent of human-induced pluripotent stem cell (hiPSC) methods and assays now offers appropriate tools to test the consequences of such compounds for neurodevelopment in vitro. In particular, hiPSCs can be used to generate cerebral organoids - self-organized structures that recapitulate the morphology and complex physiology of the developing human brain, overcoming the limitations found in 2D cell culture and experimental animal models for testing drug efficacy and side effects. For example, single-cell RNA sequencing (scRNA-seq) and electrophysiological measurements on organoids can be used to evaluate the impact of antidepressants on the transcriptome and neuronal activity signatures in developing neurons. While the analysis of large-scale transcriptomic data depends on dimensionality reduction methods, electrophysiological recordings rely on temporal data series to discriminate statistical characteristics of neuronal activity, allowing for the rigorous analysis of the effects of antidepressants and other molecules that affect the developing nervous system, especially when applied in combination with relevant human cellular models such as brain organoids.
BT - Seminars in Cell & Developmental Biology
DA - 2023-07-30
DO - 10.1016/j.semcdb.2022.09.007
LA - eng
N2 - The use of antidepressants during pregnancy benefits the mother's well-being, but the effects of such substances on neurodevelopment remain poorly understood. Moreover, the consequences of early exposure to antidepressants may not be immediately apparent at birth. In utero exposure to selective serotonin reuptake inhibitors (SSRIs) has been related to developmental abnormalities, including a reduced white matter volume. Several reports have observed an increased incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) after prenatal exposure to SSRIs such as sertraline, the most widely prescribed SSRI. The advent of human-induced pluripotent stem cell (hiPSC) methods and assays now offers appropriate tools to test the consequences of such compounds for neurodevelopment in vitro. In particular, hiPSCs can be used to generate cerebral organoids - self-organized structures that recapitulate the morphology and complex physiology of the developing human brain, overcoming the limitations found in 2D cell culture and experimental animal models for testing drug efficacy and side effects. For example, single-cell RNA sequencing (scRNA-seq) and electrophysiological measurements on organoids can be used to evaluate the impact of antidepressants on the transcriptome and neuronal activity signatures in developing neurons. While the analysis of large-scale transcriptomic data depends on dimensionality reduction methods, electrophysiological recordings rely on temporal data series to discriminate statistical characteristics of neuronal activity, allowing for the rigorous analysis of the effects of antidepressants and other molecules that affect the developing nervous system, especially when applied in combination with relevant human cellular models such as brain organoids.
PY - 2023
SP - 67
EP - 76
ST - The impact of antidepressants on human neurodevelopment
T2 - Seminars in Cell & Developmental Biology
TI - The impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools
VL - 144
SN - 1096-3634
ER -