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Risk or relief? Scientists call for more research on antidepressants and pregnancy (27 notícias)

Publicado em 19 de janeiro de 2023

Brazilian scientists propose conducting experiments using mini-brains grown in the laboratory to study the effect of drugs on fetal brain development.

Depression affects a significant proportion of pregnant women worldwide, with an estimated 10% to 16%. While most women can improve with antidepressants, the effects of these drugs on fetal brain development are not fully understood.

Brazilian researchers reviewed more than 100 scientific articles on the topic and concluded that advanced techniques such as genomics should be used to study the effects of antidepressants, especially sertraline, the most commonly prescribed antidepressant worldwide. Although the safety of using these drugs during pregnancy is supported by scientific evidence, more research is needed to fully understand their effects on the neural development of the fetus.

“Most of the publications we reviewed were reports of observational and laboratory studies using cell cultures and animals whose brain development is very different from that of humans. They do not provide sufficient data to confirm the final results,” said neuroscientist Alexandre Kihara, a researcher at the Neurogenetics Laboratory of the Federal University of ABC (UFABC) in São Bernardo do Campo, São Paulo.

“We propose an experimental trial model using human induced pluripotent stem cells [hiPSC] to investigate what happens to the development of fetal nerve cells in pregnant women during antidepressant treatment,” said Luciana Rafagni Marinho, a UFABC researcher with postdoctoral and postdoctoral qualifications in epigenetics, in vitro embryo production, and animal reproduction.

Mourinho and Kihara are the first and last authors of a review article recently published in the journal Seminars in cell and developmental biology . The research was supported by FAPESP.

Man-made pluripotent stem cells can be differentiated into brain organoids (“mini-brains”) that scientists want to use in research into neurodegenerative diseases such as Parkinson's and[{” attribute=””>Alzheimer's, and in the testing of drugs with neurological action.

“These structures can be used to test different dosages and track the development of brain cells up to the third trimester,” said Alysson Muotri, penultimate author of the article. Muotri is a neuroscientist at the University of California San Diego (UCSD) in the United States and heads a genetics laboratory that has pioneered the development of brain organoids to study autism and other neurological disorders. He is also a co-founder of Tismoo, a Brazilian biotech startup.

“We can study the organoids for up to a year, observing aspects of their development such as the morphology and electrophysiology of individual neurons or neural networks,” he explained.

To exemplify the possible advances, Marinho cited the only study that used brain organoids among the more than 100 covered by the review. “It investigated the effects of paroxetine and detected a reduction in the growth of neurites [ projections from neurons that develop into axons and dendrites to form complex circuits ] and a population of oligodendrocytes, which produce the myelin sheath around axons and are therefore important in ensuring the transmission of information throughout the nervous system,” she said.

Scientists note that whole-genome sequencing, transcript analysis, and single-cell[{” attribute=””>RNA sequencing apply to research using organoids. “The technology enables us to investigate the effects of exposure to antidepressants on different cell types, such as progenitor cells, glial cells, and neurons. This is particularly important because alterations may not be confined to neurons. We need to know all these implications,” Kihara said.

Caution is required in interpreting the findings of this kind of research. “We're not saying antidepressants shouldn't be used in pregnancy. We're proposing an experimental model and stressing the need to study their effects on neurodevelopment with the most advanced resources available so that potential alterations can be managed,” Kihara said.

Reference: “The impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools” by Luciana Simões Rafagnin Marinho, Gabrielly Maria Denadai Chiarantin, Juliane Midori Ikebara, Débora Sterzeck Cardoso, Théo Henrique de Lima-Vasconcellos, Guilherme Shigueto Vilar Higa, Mariana Sacrini Ayres Ferraz, Roberto De Pasquale, Silvia Honda Takada, Fabio Papes, Alysson R. Muotri and Alexandre Hiroaki Kihara, 15 September 2022, Seminars in Cell Developmental Biology

DOI: 10.1016/j.semcdb.2022.09.007

https://scitechdaily.com/risk-or-relief-scientists-call-for-more-research-on-antidepressants-and-pregnancy/ Risk or relief? Scientists call for more research on antidepressants and pregnancy