Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo DOI Open Access
Gerd Bicker

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1871 - 1871

Published: Feb. 7, 2022

Developmental neurotoxicity (DNT) of chemical compounds disrupts the formation a normal brain. There is impressive progress in development alternative testing methods for DNT potential chemicals, some which also incorporate invertebrate animals. This review briefly touches upon studies on genetically tractable model organisms Caenorhabditis elegans and Drosophila melanogaster about action specific developmental neurotoxicants. The functional nervous system requires precisely timed axonal pathfinding to correct cellular targets. To address this complex key event, our lab developed an assay using serum-free culture intact locust embryos. first neural pathways leg embryonic locusts are established by pair afferent pioneer neurons use guidance cues from membrane-bound diffusible semaphorin proteins. In systematic approach according recommendations testing, embryo quantifies defects navigation after exposure panel recognized test DNT. outcome indicates high predictability test-compound classification. Since pyramidal mammalian cortex gradient neurite guidance, based evolutionary conserved mechanisms, supporting its relevance cortical development.

Language: Английский

Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development DOI
Francesca Pistollato, Mauro Petrillo, Laure‐Alix Clerbaux

et al.

Reproductive Toxicology, Journal Year: 2022, Volume and Issue: 111, P. 34 - 48

Published: May 5, 2022

Language: Английский

Citations

21
Dynamic culture of cerebral organoids using a pillar/perfusion plate for the assessment of developmental neurotoxicity DOI Creative Commons

Prabha Acharya,

Sunil Shrestha, Pranav Joshi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Abstract Despite the potential toxicity of commercial chemicals to development nervous system (known as developmental neurotoxicity or DNT), conventional in vitro cell models have primarily been employed for assessment acute neuronal toxicity. On other hand, animal used DNT are not physiologically relevant due heterogenic difference between humans and animals. In addition, low-throughput, time-consuming, expensive, ethically questionable. Recently, human brain organoids emerged a promising alternative assess detrimental effects on developing brain. However, organoid culture systems several technical limitations including low throughput, lack reproducibility, insufficient maturity organoids, formation necrotic core limited diffusion nutrients oxygen. To address these issues establish predictive models, cerebral were differentiated dynamic condition unique pillar/perfusion plate, which exposed test compounds evaluate potential. The plate facilitated uniform, with improved proliferation by rapid, bidirectional flow generated digital rocker. Day 9 ascorbic acid (DNT negative) methylmercury positive) 1 3 weeks, changes morphology neural gene expression measured determine As expected, didn’t induce any expression. exposure day resulted significant Interestingly, did adverse static condition, thus highlighting importance assessment.

Language: Английский

Citations

4
How neurobehavior and brain development in alternative whole-organism models can contribute to prediction of developmental neurotoxicity DOI Creative Commons
Eva‐Maria S. Collins, Ellen V.S. Hessel, Samantha Hughes

et al.

NeuroToxicology, Journal Year: 2024, Volume and Issue: 102, P. 48 - 57

Published: March 28, 2024

Language: Английский

Citations

4
Neuronal differentiation pathways and compound-induced developmental neurotoxicity in the human neural progenitor cell test (hNPT) revealed by RNA-seq DOI
Victoria C. de Leeuw,

Conny Th.M. van Oostrom,

Paul Wackers

et al.

Chemosphere, Journal Year: 2022, Volume and Issue: 304, P. 135298 - 135298

Published: June 11, 2022

Language: Английский

Citations

18
A perspective on In vitro developmental neurotoxicity test assay results: An expert panel review DOI Creative Commons
Daland R. Juberg,

Donald A. Fox,

Patrick A. Forcelli

et al.

Regulatory Toxicology and Pharmacology, Journal Year: 2023, Volume and Issue: 143, P. 105444 - 105444

Published: July 11, 2023

For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing considerations including higher-throughput screening for DNT, reduction animal use, and cost efficiencies, development of alternative non-animal methods (NAMs) occurred; specifically, advent DNT vitro test battery (DNT IVB). SciPinion convened an expert panel address specific questions related interpretation data. The consensus was that IVB might be used during initial screening, but it is not presently a complete or surrogate approach determine whether chemical humans. By itself, does ability capture nuances complexity developing nervous system outcomes behavioral ontogeny, motor activity, sensory function, learning/memory. Presently, such landmarks cannot adequately assessed by other NAMs. (all who serve as co-authors this review) recommended additional data generation validation required before can considered application within global regulatory frameworks decision-making.

Language: Английский

Citations

10
Dynamic culture of cerebral organoids using a pillar/perfusion plate for the assessment of developmental neurotoxicity DOI

Prabha Acharya,

Sunil Shrestha, Pranav Joshi

et al.

Biofabrication, Journal Year: 2024, Volume and Issue: 17(1), P. 015001 - 015001

Published: Oct. 14, 2024

Abstract Despite the potential toxicity of commercial chemicals to development nervous system (known as developmental neurotoxicity or DNT), conventional in vitro cell models have primarily been employed for assessment acute neuronal toxicity. On other hand, animal used DNT are not physiologically relevant due heterogenic difference between humans and animals. In addition, low-throughput, time-consuming, expensive, ethically questionable. Recently, human brain organoids emerged a promising alternative assess detrimental effects on developing brain. However, organoid culture systems several technical limitations including low throughput, lack reproducibility, insufficient maturity organoids, formation necrotic core limited diffusion nutrients oxygen. To address these issues establish predictive models, cerebral were differentiated dynamic condition unique pillar/perfusion plate, which exposed test compounds evaluate potential. The plate facilitated uniform, with improved proliferation by rapid, bidirectional flow generated digital rocker. Day 9 ascorbic acid (DNT negative) methylmercury positive) 1 3 weeks, changes morphology neural gene expression measured determine As expected, did induce any expression. exposure day resulted significant Interestingly, adverse static condition, thus highlighting importance assessment.

Language: Английский

Citations

3
Advancing chemical safety assessment through an omics-based characterization of the test system-chemical interaction DOI Creative Commons
Giusy del Giudice, Giorgia Migliaccio, Nicoletta D’Alessandro

et al.

Frontiers in Toxicology, Journal Year: 2023, Volume and Issue: 5

Published: Nov. 9, 2023

Assessing chemical safety is essential to evaluate the potential risks of exposure human health and environment. Traditional methods relying on animal testing are being replaced by 3R (reduction, refinement, replacement) principle-based alternatives, mainly depending in vitro test Adverse Outcome Pathway framework. However, these approaches often focus properties compound, missing broader chemical-biological interaction perspective. Currently, lack comprehensive molecular characterization system results limited real-world representation contextualization toxicological effect under study. Leveraging omics data strengthens understanding responses different biological systems, emphasizing holistic interactions when developing methods. Here, we discuss relevance meticulous two assessment relevant scenarios how omics-based, data-driven can improve future generation alternative

Language: Английский

Citations

7
Upscaling biological complexity to boost neuronal and oligodendroglia maturation and improve in vitro developmental neurotoxicity (DNT) evaluation DOI
Carolina Nunes, Gabriela Gorczyca,

Emilio Mendoza-deGyves

et al.

Reproductive Toxicology, Journal Year: 2022, Volume and Issue: 110, P. 124 - 140

Published: April 1, 2022

Language: Английский

Citations

9
Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals DOI
Jonathan Blum, Stefan Masjosthusmann, Kristina Bartmann

et al.

SSRN Electronic Journal, Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 1, 2022

Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available only small percentage manufactured compounds. Test methods with higher throughput than current regulatory guideline methods, and improved relevance urgently needed. We therefore explored feasibility hazard assessment based on new approach (NAMs). An in vitro battery (IVB) was assembled ten individual NAMs that had been developed during past years to probe effects various fundamental neurodevelopmental processes. All assays used neural cells at different developmental stages. This allowed us assess disturbances of: (i) proliferation progenitor (NPC); (ii) migration crest cells, radial glia neurons oligodendrocytes; (iii) differentiation NPC into (iv) neurite outgrowth peripheral central neurons. In parallel, cytotoxicity measures were obtained. The concentration-dependent screening reliable biostatistical processing complex multi-dimensional set 120 test compounds, containing subsets pre-defined positive negative provided alerts (hit or borderline) 24 28 known toxicants (82% sensitivity), none 17 controls. Based results this screen project, strategies how IVB may be context risk scenarios employing integrated approaches testing (IATA).

Language: Английский

Citations

9
Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment DOI Creative Commons
G. Jean Harry, Sandra J. McBride,

Shannah K. Witchey

et al.

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

Published: Feb. 25, 2022

With the appreciation that behavior represents integration and complexity of nervous system, neurobehavioral phenotyping assessment has seen a renaissance over last couple decades, resulting in robust database on rodent performance within various testing paradigms, possible associations with human disorders, therapeutic interventions. The interchange data across other test modalities multiple model systems advanced our understanding fundamental biology mechanisms associated normal functions alterations system. While there is demonstrated value power assessments for examining due to genetic manipulations, maternal factors, early development environment, applied use assess environmental neurotoxicity continues come under question as whether sensitive endpoint assessment. Why tool neuroscientist yet, not when used pre-clinical or chemical studies? Applying new paradigms evidence biological basis requires expertise refinement how such experiments are conducted minimize variability maximize information. This review presents relevant issues methods conduct test, sources variability, experimental design, analysis, interpretation, reporting. It beneficial critical limitations they translate vivo environment considers need integrate disciplines best value. proposes behavioral subtle pronounced differences will facilitate obtained approaches address translation.

Language: Английский

Citations

8