Abstract
Increasing evidence indicates that developmental exposure to nonylphenol (NP) causes damage to the central nervous system (CNS). As the most unique and primary component of neuron, axon is an essential structure for the CNS function. Here, we investigated whether developmental exposure to NP affected rat axonal development in vivo and in vitro. Our results showed that developmental exposure to NP 10, 50, and 100 mg/(kg day) caused an obvious decrease in axonal length and density in the hippocampus. Developmental exposure to NP also altered the expression of CRMP-2 and p-CRMP-2, and activated Wnt-Dvl-GSK-3β cascade in the hippocampus, the crucial signaling that regulates axonal development. Even months after the exposure, impairment of axonal growth and alteration of this cascade were not fully restored. In the primary cultured neurons, 30, 50, and 70 μM NP treatment decreased axonal length and impaired axonal function. Similar to in vivo results, it also activated Wnt-Dvl-GSK-3β cascade in cultured neurons. SB-216763, a specific GSK-3β inhibitor, recovered the shortening of axon and the impairment of axonal function induced by NP. Taken together, our results support the idea that exposure to NP induces axonal injury in the developing neurons. Furthermore, the activation of Wnt-Dvl-GSK-3β cascade contributes to the axonal injury induced by NP.
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Abbreviations
- BBB:
-
Blood–brain barrier
- CNS:
-
Central nervous system
- CRMP-2:
-
Collapsin response mediator protein-2
- DMSO:
-
Dimethyl sulfoxide
- Dvl:
-
Dishevelled
- GD:
-
Gestational day
- GSK-3β:
-
Glycogen synthase kinase-3β
- NP:
-
Nonylphenol
- NPnEO:
-
Nonylphenol ethoxylates
- PB:
-
Placental barrier
- PND:
-
Postnatal day
- POPs:
-
Persistent organic pollutants
- p-CRMP-2:
-
Phosphorylated CRMP-2
- p-GSK-3β:
-
Phosphorylated GSK-3β
- SB:
-
SB-216763
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Acknowledgements
This work was supported by Natural Science Foundation of Liaoning Province, China (Grant number: 201602865), Program for Liaoning Innovative Research Team in University (Grant number: LT2015028), and Liaoning Revitalization Talents Program (Grant number: XLYC1807225).
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Supplementary material 1 (TIFF 7994 kb). Schematic overview of involvement of Wnt-Dvl-GSK-3β cascade in NP-induced axonal injury
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Li, S., You, M., Chai, W. et al. Developmental exposure to nonylphenol induced rat axonal injury in vivo and in vitro. Arch Toxicol 93, 2673–2687 (2019). https://doi.org/10.1007/s00204-019-02536-0
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DOI: https://doi.org/10.1007/s00204-019-02536-0