Novel Strategy to Assess the Neurotoxicity of Organic Solvents Such as Glycol Ethers: Protocol for Combining In Vitro and In Silico Methods With Human-Controlled Exposure Experiments (Preprint) DOI
Nancy B. Hopf, Laura Suter‐Dick, Jörg Huwyler

et al.

Published: June 26, 2023

BACKGROUND Chemicals are not required to be tested systematically for their neurotoxic potency, although they may contribute the development of several neurological diseases. The absence systematic testing partially explained by current Organisation Economic Co-operation and Development (OECD) Test Guidelines, which rely on animal experiments that expensive, laborious, ethically debatable. Therefore, it is important understand risks exposed workers general population domestic products. In this study, we propose a strategy test neurotoxicity solvents using commonly used glycol ethers as case study. OBJECTIVE This study aims provide can regulatory agencies industries rank according demonstrate use toxicokinetic modeling predict air concentrations below no observed adverse effect (NOAECs) human determined in vitro assays. METHODS proposed focuses complex 3D brain model (BrainSpheres) derived from human-induced pluripotent stem cells (hiPSCs). accompanied vivo, vitro, silico models blood-brain barrier (BBB) liver metabolism. data integrated into model. Internal predicted compared with results vivo human-controlled exposure validation. then reverse dosimetry concentrations, leading lower than NOAECs hiPSC-derived These predictions will protection exposures. RESULTS Swiss Centre Applied Human Toxicology funded project, commencing January 2021. Ethics Committee approval was obtained November 16, 2022. Zebrafish methods started February 2021, whereas recruitment volunteers 2022 after COVID-19 pandemic–related restrictions were lifted. We anticipate able 2026 6 propylene based incorporating metabolism, BBB leakage parameters, toxicity. CONCLUSIONS great interest chemical needing seeking novel solutions develop risk assessments. It protecting health deleterious effects environmental chemicals. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/50300

Language: Английский

Proteomic-miRNA Biomics Profile Reveals 2D Cultures of Human iPSC-Derived Neural Progenitor Cells More Sensitive than 3D Spheroid System Against the Experimental Exposure to Arsenic DOI
Renu Negi, Ankita Srivastava, Ankur Kumar Srivastava

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5754 - 5770

Published: Jan. 16, 2024

Language: Английский

Citations

2
Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro? DOI Creative Commons
А. Б. Салмина, Olga P. Alexandrova, Anton S. Averchuk

et al.

Journal of Tissue Engineering, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

In vitro modeling of brain tissue is a promising but not yet resolved problem in modern neurobiology and neuropharmacology. Complexity the structure diversity cell-to-cell communication (patho)physiological conditions make this task almost unachievable. However, establishment novel models would ultimately lead to better understanding development-associated or experience-driven plasticity, designing efficient approaches restore aberrant functioning. The main goal review summarize available data on methodological that are currently use, identify most prospective trends development neurovascular unit, blood-brain barrier, blood-cerebrospinal fluid neurogenic niche models. manuscript focuses regulation adult neurogenesis, cerebral microcirculation fluids dynamics should be reproduced 4D mimic its alterations pathology. We discuss critical for studying deciphering individual person-specific trajectory aging, testing new drug candidates

Language: Английский

Citations

2
High-Throughput Screening Assay for Detecting Drug-Induced Changes in Synchronized Neuronal Oscillations and Potential Seizure Risk Based on Ca2+ Fluorescence Measurements in Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neuronal 2D and 3D Cultures DOI Creative Commons

Hua-Rong Lu,

Manabu Seo,

Mohamed Kreir

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 958 - 958

Published: March 21, 2023

Drug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence late development results increased costs, human risk, delayed market availability of novel therapeutics. Therefore, there an urgent need biologically relevant, vitro high-throughput screening assays (HTS) to predict potential risks drug-induced early discovery. We investigated changes neural Ca2+ oscillations, using fluorescent dyes as indicator hiPSC-derived neurons co-cultured with primary astrocytes both 2D 3D forms. The dynamics synchronized neuronal calcium oscillations were measured FDSS kinetics reader. Drug responses recorded neuron/primary astrocyte co-cultures positive controls (4-aminopyridine kainic acid) negative control (acetaminophen). Subsequently, blinded tests carried out 25 drugs known clinical incidence. Positive predictive value (accuracy) based on peak number among reference was 91% vs. 45% hiPSC-neuron/primary co-cultures. These data suggest that alter activity may have risk seizures can be identified high accuracy HTS approach measurements 2D.

Language: Английский

Citations

5
Direct Cell Reprogramming and Phenotypic Conversion: An Analysis of Experimental Attempts to Transform Astrocytes into Neurons in Adult Animals DOI Creative Commons

Rachel Dennison,

Esteban Usuga,

Harriet Chen

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 618 - 618

Published: Feb. 14, 2023

Central nervous system (CNS) repair after injury or disease remains an unresolved problem in neurobiology research and unmet medical need. Directly reprogramming converting astrocytes to neurons (AtN) adult animals has been investigated as a potential strategy facilitate brain spinal cord recovery advance fundamental biology. Conceptually, AtN strategies rely on forced expression repression of lineage-specific transcription factors make endogenous become “induced neurons” (iNs), presumably without re-entering any pluripotent multipotent states. The AtN-derived cells have reported manifest certain neuronal functions vivo. However, this approach raised many new questions alternative explanations regarding the biological features end products (e.g., iNs versus neuron-like cells, neural functional changes, etc.), developmental biology underpinnings, neurobiological essentials. For paper per se, we proposed draw unconventional distinction between direct cell conversion reprogramming, relative somatic nuclear transfer, based experimental methods utilized initiate transformation process, aiming promote more in-depth mechanistic exploration. Moreover, summarized current tactics employed for induction, comparisons bench endeavors concerning outcome tangibility, discussion issues published protocols. Lastly, urgency clearly define/devise theoretical frameworks, bases, specifics experimentally validate primary data studies was highlighted.

Language: Английский

Citations

5
Establishment of human pluripotent stem cell-derived cortical neurosphere model to study pathomechanisms and chemical toxicity in Kleefstra syndrome DOI Creative Commons
Andrea Balogh,

Mária Bódi-Jakus,

Vivien Réka Karl

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 29, 2024

Language: Английский

Citations

1
Modulation of Ca2+ oscillation following ischemia and nicotinic acetylcholine receptors in primary cortical neurons by high-throughput analysis DOI Creative Commons
Tsutomu Sasaki,

Sunao Hisada,

Hideaki Kanki

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 12, 2024

Calcium oscillations in primary neuronal cultures and iPSCs have been employed to investigate arrhythmogenicity epileptogenicity drug development. Previous studies demonstrated that Ca

Language: Английский

Citations

1
Enhanced electrophysiological activity and neurotoxicity screening of environmental chemicals using 3D neurons from human neural precursor cells purified with PSA-NCAM DOI Creative Commons

Mi‐Sun Choi,

Se‐Myo Park, Soo‐Jin Kim

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 280, P. 116516 - 116516

Published: May 31, 2024

The assessment of neurotoxicity for environmental chemicals is utmost importance in ensuring public health and safety. Multielectrode array (MEA) technology has emerged as a powerful tool assessing disturbances the electrophysiological activity. Although human embryonic stem cell (hESC)-derived neurons have been used MEA screening, obtaining substantial sufficiently active population from hESCs remains challenging. In this study, we successfully differentiated large neuronal precursor cells (hNPC) purified using polysialylated neural adhesion molecule (PSA-NCAM), referred to hNPC

Language: Английский

Citations

0
Human-Induced Pluripotent Stem Cell-Derived Neural Organoids as a Novel In Vitro Platform for Developmental Neurotoxicity Assessment DOI Open Access

Tsunehiko Hongen,

Kenta Sakai,

Tomohiro Ito

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12523 - 12523

Published: Nov. 21, 2024

There has been a recent drive to replace in vivo studies with vitro the field of toxicity testing. Therefore, instead conventional animal or planar cell culture models, there is an urgent need for systems whose conditions can be strictly controlled, including cell-cell interactions and sensitivity low doses chemicals. Neural organoids generated from human-induced pluripotent stem cells (iPSCs) are promising platform modeling human brain development. In this study, we developed new tool based on various iPSCs study predict chemical-induced humans. The model displayed several neurodevelopmental features showed good reproducibility, comparable that previously published models. results revealed basic fibroblast growth factor plays key role formation embryoid body, as well complex neural networks higher-order structures such layered stacking. Using organoid pesticide toxicities were assessed. Cells treated concentrations rotenone underwent apoptosis greater extent than those high rotenone. Morphological changes associated development progenitor observed after exposure chlorpyrifos. These findings suggest neuronal mimic developmental processes occurring nerves useful evaluating drug efficacy, safety, toxicity.

Language: Английский

Citations

0
Editorial: Methods and protocols in neurotoxicology DOI Creative Commons
Ellen Fritsche, Marta Barenys, Helena T. Högberg

et al.

Frontiers in Toxicology, Journal Year: 2022, Volume and Issue: 4

Published: Oct. 21, 2022

EDITORIAL article Front. Toxicol., 21 October 2022Sec. Neurotoxicology Volume 4 - 2022 | https://doi.org/10.3389/ftox.2022.1031667

Language: Английский

Citations

1
Novel Strategy to Assess the Neurotoxicity of Organic Solvents Such as Glycol Ethers: Protocol for Combining In Vitro and In Silico Methods With Human-Controlled Exposure Experiments (Preprint) DOI
Nancy B. Hopf, Laura Suter‐Dick, Jörg Huwyler

et al.

Published: June 26, 2023

BACKGROUND Chemicals are not required to be tested systematically for their neurotoxic potency, although they may contribute the development of several neurological diseases. The absence systematic testing partially explained by current Organisation Economic Co-operation and Development (OECD) Test Guidelines, which rely on animal experiments that expensive, laborious, ethically debatable. Therefore, it is important understand risks exposed workers general population domestic products. In this study, we propose a strategy test neurotoxicity solvents using commonly used glycol ethers as case study. OBJECTIVE This study aims provide can regulatory agencies industries rank according demonstrate use toxicokinetic modeling predict air concentrations below no observed adverse effect (NOAECs) human determined in vitro assays. METHODS proposed focuses complex 3D brain model (BrainSpheres) derived from human-induced pluripotent stem cells (hiPSCs). accompanied vivo, vitro, silico models blood-brain barrier (BBB) liver metabolism. data integrated into model. Internal predicted compared with results vivo human-controlled exposure validation. then reverse dosimetry concentrations, leading lower than NOAECs hiPSC-derived These predictions will protection exposures. RESULTS Swiss Centre Applied Human Toxicology funded project, commencing January 2021. Ethics Committee approval was obtained November 16, 2022. Zebrafish methods started February 2021, whereas recruitment volunteers 2022 after COVID-19 pandemic–related restrictions were lifted. We anticipate able 2026 6 propylene based incorporating metabolism, BBB leakage parameters, toxicity. CONCLUSIONS great interest chemical needing seeking novel solutions develop risk assessments. It protecting health deleterious effects environmental chemicals. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/50300

Language: Английский

Citations

0