ArticleNeurotoxicology2019
Huntington's disease associated resistance to Mn neurotoxicity is neurodevelopmental stage and neuronal lineage dependent.
Article in Neurotoxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Emergent latent neurotoxic effects of manganese following nominal chronic exposures in human stem cell and Caenorhabditis elegans models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Prolonged duration induces divergent transcriptomic responses to manganese, distinct from concentration effects, in an SH-SY5Y neurotoxicity model.Neurotoxicology · 2026Article
- Unconventional Non-rodent Models in Neurological Research: Exploring New Paths to Translational Insights.Journal of molecular neuroscience : MN · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Expanded ATXN1 alters transcription and calcium signaling in SCA1 human motor neurons differentiated from induced pluripotent stem cells.Neurobiology of disease · 2024Article
- Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington's Disease.Cells · 2024Review
- Copper enhances aggregational toxicity of mutant huntingtin in a Drosophila model of Huntington's Disease.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
- Impaired Reorganization of Centrosome Structure Underlies Human Infantile Dilated Cardiomyopathy.Circulation · 2023Article
- Impaired XK recycling for importing manganese underlies striatal vulnerability in Huntington's disease.The Journal of cell biology · 2022Article
- Endosomal recycling defects link Huntington's disease with McLeod syndrome.The Journal of cell biology · 2022Article
- Exposing the role of metals in neurological disorders: a focus on manganese.Trends in molecular medicine · 2022Review
- Novel test strategies for in vitro seizure liability assessment.Expert opinion on drug metabolism & toxicology · 2021Review
- Single cell RNA sequencing detects persistent cell type- and methylmercury exposure paradigm-specific effects in a human cortical neurodevelopmental model.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Article
- Review
- Environmentally relevant developmental methylmercury exposures alter neuronal differentiation in a human-induced pluripotent stem cell model.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Article
- Dietary Supplementation of EGF Ameliorates the Negatively Effects of LPS on Early-Weaning Piglets: From Views of Growth Performance, Nutrient Digestibility, Microelement Absorption and Possible Mechanisms.Animals : an open access journal from MDPI · 2021Article
- Going Back and Forth: Episomal Vector Reprogramming of Peripheral Blood Mononuclear Cells to Induced Pluripotent Stem Cells and Subsequent Differentiation into Cardiomyocytes and Neuron-Astrocyte Co-cultures.Cellular reprogramming · 2020Article
- Manganese-induced neurodegenerative diseases and possible therapeutic approaches.Expert review of neurotherapeutics · 2020Review
- Identification of a selective manganese ionophore that enables nonlethal quantification of cellular manganese.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Manganese (Mn) is essential for neuronal health but neurotoxic in excess. Mn levels vary across brain regions and neurodevelopment. While Mn requirements during infanthood and childhood are significantly higher than in adulthood, the relative vulnerability to excess extracellular Mn across human neuronal developmental time and between distinct neural lineages is unknown. Neurological disease is associated with changes in brain Mn homeostasis and pathology associated with Mn neurotoxicity is not uniform across brain regions. For example, mutations associated with Huntington's disease (HD) decrease Mn bioavailability and increase resistance to Mn cytotoxicity in human and mouse striatal neuronal progenitors. Here, we sought to compare the differences in Mn cytotoxicity between control and HD human-induced pluripotent stem cells (hiPSCs)-derived neuroprogenitor cells (NPCs) and maturing neurons. We hypothesized that there would be differences in Mn sensitivity between lineages and developmental stages. However, we found that the different NPC lineage specific media substantially influenced Mn cytotoxicity in the hiPSC derived human NPCs and did so consistently even in a non-human cell line. This limited the ability to determine which human neuronal sub-types were more sensitive to Mn. Nonetheless, we compared within neuronal subtypes and developmental stage the sensitivity to Mn cytotoxicity between control and HD patient derived neuronal lineages. Consistent with studies in other striatal model systems the HD genotype was associated with resistance to Mn cytotoxicity in human striatal NPCs. In addition, we report an HD genotype-dependent resistance to Mn cytotoxicity in cortical NPCs and hiPSCs. Unexpectedly, the HD genotype conferred increased sensitivity to Mn in early post-mitotic midbrain neurons but had no effect on Mn sensitivity in midbrain NPCs or post-mitotic cortical neurons. Overall, our data suggest that sensitivity to Mn cytotoxicity is influenced by HD genotype in a human neuronal lineage type and stage of development dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.