Review
Biology
Magdalini Sachana, Timothy J. Shafer, Andrea Terron
Summary: Recognizing the current DNT testing paradigm is not suitable for assessing a large number of chemicals, scientific advances have been made in alternative methods to evaluate chemical interactions with the developing nervous system without using animals. The OECD provides internationally harmonised guidelines based on cellular models for testing and assessing chemicals for DNT. To address challenging endpoints like DNT, the OECD has been developing integrated approaches for testing and assessment, which rely on a combination of different data layers and mechanistic knowledge.
Review
Biochemistry & Molecular Biology
Nemanja Useinovic, Stefan Maksimovic, Michelle Near, Nidia Quillinan, Vesna Jevtovic-Todorovic
Summary: Since its invention, general anesthesia has been crucial in modern surgery. However, concerns about the negative effects of anesthetics on the developing brain have been raised through preclinical studies and clinical evidence. Further understanding the molecular basis of anesthesia-induced neurotoxicity is important for developing protective strategies and ensuring safe usage during critical stages of brain development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Food Science & Technology
SunHwa Jeong, Seon-Mi Park, Na Rea Jo, Jin-Sook Kwon, Jimin Lee, KangMin Kim, Seon Myeong Go, Lian Cai, Dohee Ahn, Sung Duck Lee, Sang-Hwan Hyun, Kyung-Chul Choi, Eui-Bae Jeung
Summary: This study successfully improved the predictability of the developmental neurotoxicity test (DNT) method and established a second-generation discriminant function (2nd GDF) using cell assays and mobility evaluation. The results demonstrated that the method accurately classified the toxicity of the substances and showed transferability, reproducibility, and accuracy.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Food Science & Technology
Yan Zhang, Fei-Fei Yang, Huan Chen, Yao-Dong Qi, Jian-Yong Si, Qing Wu, Yong-Hong Liao
Summary: This study aimed to analyze pyrrolizidine alkaloids in E. fortunei herbs and evaluate their effects on neural progenitor cells. Using LC-MS/MS, 8 PAs were identified with potential negative impacts on cell viability and oligodendrogenesis.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Environmental Sciences
Hehai Huang, Yuan Jin, Chuanying Chen, Meiyao Feng, Qing Wang, Daochuan Li, Wen Chen, Xiumei Xing, Dianke Yu, Yongmei Xiao
Summary: This study developed a pathway-based MOA for assessing Pb-induced neurotoxicity using Comparative Toxicogenomic Database and Ingenuity Pathway Analysis. The neuroinflammation signaling pathway was identified as the core toxicity pathway, with AHR activation as the first key event in the MOA framework.
ENVIRONMENTAL RESEARCH
(2021)
Article
Environmental Sciences
Hannes Reinwald, Julia Alvincz, Gabriela Salinas, Christoph Schafers, Henner Hollert, Sebastian Eilebrecht
Summary: This study characterized the transcriptomic responses to six insecticides in zebrafish embryos, aiming to identify biomarker candidates for specific modes of action. Abamectin showed the most unique signature related to lipid metabolic processes. Differentially expressed genes after imidacloprid exposure were primarily associated with immune system and inflammation. The findings provide insights into early molecular events in response to the analyzed modes of action.
Article
Biochemistry & Molecular Biology
Seonguk Yang, Seulah Lee, Yujeong Lee, Jung-Hyun Cho, Sou Hyun Kim, Eun-Sol Ha, Young-Suk Jung, Hae Young Chung, Min-Soo Kim, Hyung Sik Kim, Seung-Cheol Chang, Kyung-Jin Min, Jaewon Lee
Summary: This study investigated the neurotoxicity of polystyrene nanoparticles on neural progenitor cells and hippocampal neurogenesis. The results showed that cationic amine-modified polystyrene had cytotoxic effects, while anionic carboxylate-modified polystyrene and neutral nanoparticles did not. Cationic polystyrene nanoparticles caused mitochondrial dysfunction, energy depletion, and cellular senescence. In vivo studies on mice demonstrated impaired hippocampal neurogenesis and memory retention after exposure to cationic polystyrene nanoparticles.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Britt Mossink, Moritz Negwer, Dirk Schubert, Nael Nadif Kasri
Summary: This review discusses the important role of chromatin remodelers in neurodevelopment, indicating that gene mutations in NDDs are related to epigenetics, which is an important pathogenic pathway between these disorders. Over time, chromatin remodeling defects can result in impaired brain circuit establishment, especially in glutamatergic neurons, GABAergic neurons, and glia cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Kimberly J. Berry, Uma Chandran, Fangping Mu, Dinesh K. Deochand, T. Lei, Miriam Pagin, Silvia K. Nicolis, A. Paula Monaghan-Nichols, Inez Rogatsky, Donald B. DeFranco
Summary: Prenatal exposure to synthetic glucocorticoids (sGCs) can reprogram brain development and increase the risk of adverse neurodevelopmental outcomes in the fetus. In a mouse model, researchers found that sGCs caused sexually dimorphic changes in the transcriptome of neural stem and progenitor cells (NSPCs) in the embryonic brain. By analyzing multiple genome-wide assays, they discovered that glucocorticoid receptor (GR) preferentially binds to specific regions of accessible chromatin to influence gene programming and cell fate decisions in NSPCs. They also identified SOX2 as a transcription factor that affects the genomic response of certain GR target genes to sGCs.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Toxicology
Robert P. Baines, Kathryn Wolton, Christopher R. L. Thompson
Summary: This research explores the potential of the eukaryotic social amoeba Dictyostelium discoideum as an alternative nonanimal model for DART testing. By developing assays for high-throughput screening of toxicity, it was shown that D. discoideum can broadly predict mammalian toxicity. Additionally, this system can be used for functional genomic screens to compare the molecular modes of action of different compounds.
TOXICOLOGICAL SCIENCES
(2021)
Article
Genetics & Heredity
Meret Wegler, Xiangbin Jia, Marielle Alders, Arjan Bouman, Jia Chen, Xinyu Duan, Julie L. Lauzon, Inge B. Mathijssen, Heinrich Sticht, Steffen Syrbe, Senwei Tan, Hui Guo, Rami Abou Jamra
Summary: This study investigated the role of PABPC1 in developmental delay (DD). The researchers found that mutations in PABPC1 can lead to symptoms such as DD, expressive speech delay, and autistic features. These mutations affect the interaction between PABPC1 and PAIP2 and result in decreased proliferation of neural progenitor cells. The findings suggest that interference with translation initiation and impaired neurogenesis in cortical development may contribute to DD.
GENETICS IN MEDICINE
(2022)
Article
Cell Biology
Jordis Klose, Lu Li, Melanie Pahl, Farina Bendt, Ulrike Hubenthal, Christian Jungst, Patrick Petzsch, Astrid Schauss, Karl Kohrer, Ping Chung Leung, Chi Chiu Wang, Katharina Koch, Julia Tigges, Xiaohui Fan, Ellen Fritsche
Summary: Adverse Outcome Pathways (AOPs) provide a framework for linking toxicological mechanistic information with adverse health effects. This study combines phenotypic and transcriptomic analyses to assess the developmental neurotoxicity (DNT) hazards of two Chinese herbal medicines and gain insights into their modes-of-action. The results demonstrate the power of this approach in elucidating compounds' MoA and incorporating them into novel or existing AOPs for a better understanding of DNT risk in a regulatory context.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Pawel Staszek, Urszula Krasuska, Katarzyna Ciacka, Agnieszka Gniazdowska
Summary: Plants' allelopathic interactions play a crucial role in shaping plant communities, with a lack of data on the molecular mode of action of allelotoxins. The development of -omic techniques provides an opportunity to study ROS-dependent changes induced by allelochemicals, highlighting the importance of ROS metabolism as an indirect mode of action of allelochemicals.
Article
Reproductive Biology
Chiara Cervetto, Francesca Pistollato, Sarah Amato, Emilio Mendoza-de Gyves, Anna Bal-Price, Guido Maura, Manuela Marcoli
Summary: Human induced pluripotent stem cell-derived neural stem cells have been considered suitable for assessing developmental neurotoxicity caused by environmental chemicals. The currently proposed in vitro battery for regulatory neurotoxicity testing includes various assays for key neurodevelopmental processes, but lacks methods to measure interference with neurotransmitter release or clearance. This study used a HPLC-based method to measure neurotransmitter release in hiPSC-derived NSCs, and showed that glutamate release plays a role in maintaining extracellular glutamate levels. The authors conclude that analysis of neurotransmitter release should be included in the battery of in vitro assays for developmental neurotoxicity testing.
REPRODUCTIVE TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Nanxi Bi, Jinjun Ding, Rongxin Zou, Xiaozhen Gu, Zhi-Hua Liu, Hui-Li Wang
Summary: The study revealed that exposure to BPA resulted in impaired spatial memory in Thy1-Cre mice, possibly due to the detrimental effects on the excitatory neural circuits of CA3-CA1 and EC-CA1.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)