Related Experiment Video
Updated: Dec 25, 2025
In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity
Cherish A Taylor1, Karin Tuschl2,3, Merle M Nicolai4
1Division of Pharmacology & Toxicology, College of Pharmacy, Institute for Cellular & Molecular Biology, and Institute for Neuroscience, The University of Texas at Austin, Austin, TX, USA.
Abstract:
Manganese is an essential metal, but elevated brain Mn concentrations produce a parkinsonian-like movement disorder in adults and fine motor, attentional, cognitive, and intellectual deficits in children. Human Mn neurotoxicity occurs owing to elevated exposure from occupational or environmental sources, defective excretion (e.g., due to cirrhosis), or loss-of-function mutations in the Mn transporters solute carrier family 30 member 10 or solute carrier family 39 member 14. Animal models are essential to study Mn neurotoxicity, but in order to be translationally relevant, such models should utilize environmentally relevant Mn exposure regimens that reproduce changes in brain Mn concentrations and neurological function evident in human patients. Here, we provide guidelines for Mn exposure in mice, rats, nematodes, and zebrafish so that brain Mn concentrations and neurobehavioral sequelae remain directly relatable to the human phenotype.
Insights
Elevated manganese (Mn) in the brain causes Parkinson
Area of Science:
- Neurotoxicology
- Environmental Health
- Comparative Neuroscience
Background:
- Manganese (Mn) is essential but toxic at elevated concentrations, causing Parkinson's-like symptoms and cognitive deficits in humans.
- Human manganese neurotoxicity results from occupational/environmental exposure, impaired excretion, or genetic defects in Mn transporters (SLC30A10, SLC39A14).
- Translational relevance of animal models requires environmentally relevant exposure mimicking human Mn brain changes and neurological effects.
Purpose of the Study:
- To establish guidelines for manganese (Mn) exposure in animal models (mice, rats, nematodes, zebrafish).
- To ensure that Mn exposure regimens in animal models accurately reflect human Mn neurotoxicity.
- To facilitate direct comparison of neurobehavioral outcomes between animal models and human patients.
Main Methods:
- Development of standardized manganese (Mn) exposure protocols for mice, rats, nematodes, and zebrafish.
- Focus on environmentally relevant exposure levels and durations.
- Assessment of resulting brain Mn concentrations and neurobehavioral sequelae.
Main Results:
- Guidelines provided for Mn exposure in mice, rats, nematodes, and zebrafish.
- Protocols aim to reproduce human-relevant brain Mn concentrations.
- Neurobehavioral outcomes in models are designed to correlate with human Mn neurotoxicity phenotypes.
Conclusions:
- Standardized Mn exposure guidelines enhance the translational validity of animal models for neurotoxicity research.
- These guidelines enable more accurate prediction of human Mn neurotoxicity based on animal studies.
- Facilitates research into mechanisms and potential treatments for manganese-induced neurological disorders.
