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Your search keyword '"Bruno S. Guerra"' showing total 3 results
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3 results on '"Bruno S. Guerra"'

1. Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment

Author

Jason W. Adams, Annabelle Vinokur, Janaína S. de Souza, Charles Austria, Bruno S. Guerra, Roberto H. Herai, Karl J. Wahlin, and Alysson R. Muotri

Subjects
CP: Neuroscience, CP: Developmental biology, Biology (General), QH301-705.5
Abstract

Summary: Individuals with Williams syndrome (WS), a neurodevelopmental disorder caused by hemizygous loss of 26–28 genes at 7q11.23, characteristically portray a hypersocial phenotype. Copy-number variations and mutations in one of these genes, GTF2I, are associated with altered sociality and are proposed to underlie hypersociality in WS. However, the contribution of GTF2I to human neurodevelopment remains poorly understood. Here, human cellular models of neurodevelopment, including neural progenitors, neurons, and three-dimensional cortical organoids, are differentiated from CRISPR-Cas9-edited GTF2I-knockout (GTF2I-KO) pluripotent stem cells to investigate the role of GTF2I in human neurodevelopment. GTF2I-KO progenitors exhibit increased proliferation and cell-cycle alterations. Cortical organoids and neurons demonstrate increased cell death and synaptic dysregulation, including synaptic structural dysfunction and decreased electrophysiological activity on a multielectrode array. Our findings suggest that changes in synaptic circuit integrity may be a prominent mediator of the link between alterations in GTF2I and variation in the phenotypic expression of human sociality.

Published
2024
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2. Impact of alcohol exposure on neural development and network formation in human cortical organoids

Author

Jason W. Adams, Priscilla D. Negraes, Justin Truong, Timothy Tran, Ryan A. Szeto, Bruno S. Guerra, Roberto H. Herai, Carmen Teodorof-Diedrich, Stephen A. Spector, Miguel Del Campo, Kenneth L. Jones, Alysson R. Muotri, and Cleber A. Trujillo

Subjects
Proteomics, Neurogenesis, Intellectual and Developmental Disabilities (IDD), Medical and Health Sciences, Cellular and Molecular Neuroscience, Substance Misuse, Alcohol Use and Health, Pregnancy, Humans, 2.1 Biological and endogenous factors, Conditions Affecting the Embryonic and Fetal Periods, Aetiology, Molecular Biology, Fetal Alcohol Spectrum Disorders (FASD), Cerebral Cortex, Pediatric, Psychiatry, Ethanol, Psychology and Cognitive Sciences, Neurosciences, Perinatal Period - Conditions Originating in Perinatal Period, Biological Sciences, Stem Cell Research, Brain Disorders, Organoids, Psychiatry and Mental health, Alcoholism, Good Health and Well Being, Fetal Alcohol Spectrum Disorders, Prenatal Exposure Delayed Effects, Neurological, Female, Biotechnology
Abstract

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

Published
2023

3. Impact of alcohol exposure on neural development and network formation in human cortical organoids

Author

Jason W, Adams, Priscilla D, Negraes, Justin, Truong, Timothy, Tran, Ryan A, Szeto, Bruno S, Guerra, Roberto H, Herai, Carmen, Teodorof-Diedrich, Stephen A, Spector, Miguel, Del Campo, Kenneth L, Jones, Alysson R, Muotri, and Cleber A, Trujillo

Abstract

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

Published
2021

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