03230nas a2200493   4500000000100000000000100001008004100002260001500043653000900058653001200067653002600079653002900105653002900134653002200163653001000185653001100195653001000206653001100216653002000227653002600247653003100273653001400304653001400318653004400332653002500376653001800401100003700419700003900456700002700495700002900522700004000551700003400591700003300625700002400658700002400682700001600706700002200722700002900744245009900773300001000872490000800882520183200890022001402722       2023                            d  c2023-07-3010aADHD10aAnimals10aAntidepressive Agents10aAutism Spectrum Disorder10aAutism Spectrum Disorder10aAutistic Disorder10aBrain10aFemale10aHiPSC10aHumans10aInfant, Newborn10aLeukoencephalopathies10aMajor depressive disorders10aorganoids10aPregnancy10aSelective Serotonin Reuptake Inhibitors10aSingle-cell analyses10aTranscriptome1 aLuciana Simões Rafagnin Marinho1 aGabrielly Maria Denadai Chiarantin1 aJuliane Midori Ikebara1 aDébora Sterzeck Cardoso1 aThéo Henrique de Lima-Vasconcellos1 aGuilherme Shigueto Vilar Higa1 aMariana Sacrini Ayres Ferraz1 aRoberto De Pasquale1 aSilvia Honda Takada1 aFabio Papes1 aAlysson R. Muotri1 aAlexandre Hiroaki Kihara00aThe impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools  a67-760 v1443 aThe 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.  a1096-3634