PUBLICATION
Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging
- Authors
- Xu, Y., Liu, J., Tian, Y., Wang, Z., Song, Z., Li, K., Zhang, S., Zhao, H.
- ID
- ZDB-PUB-221018-59
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(19): (Journal)
- Registered Authors
- Keywords
- Wnt/β-catenin signaling pathway, cadmium (Cd), in vivo two-photon neuroimaging, microglia, neurobehavioral tests, neurotoxicity, zebrafish
- MeSH Terms
-
- Animals
- Cadmium*/toxicity
- Ecosystem
- Environmental Pollutants*/pharmacology
- Follow-Up Studies
- Neuroimaging
- Neuroinflammatory Diseases*/chemically induced
- Neurotoxicity Syndromes*/etiology
- Wnt Signaling Pathway*
- Zebrafish/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 36232737 Full text @ Int. J. Mol. Sci.
Citation
Xu, Y., Liu, J., Tian, Y., Wang, Z., Song, Z., Li, K., Zhang, S., Zhao, H. (2022) Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging. International Journal of Molecular Sciences. 23(19):.
Abstract
Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/β-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/β-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/β-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of β-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/β-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping