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Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene
Chong Liu1, Yan Zhao2, Wei Zhang1,3
1MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Department of Cell Biology, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Abstract:
The impact of polystyrene microplastics (PS-MPs) on the nervous system has been documented in the literature. Numerous studies have demonstrated that the activation of the epidermal growth factor receptor 4 (ErbB4) is crucial in neuronal injury and regeneration processes. This study investigated the role of targeted activation of ErbB4 receptor through a small molecule agonist, 4-bromo-1-hydroxy-2-naphthoic acid (C11H7BrO3, E4A), in mitigating PS-MPs-induced neuronal injury. The findings revealed that targeted activation of ErbB4 receptor significantly ameliorated cognitive behavioral deficits in mice exposed to PS-MPs. Furthermore, E4A treatment upregulated the expression of dedicator of cytokinesis 3 (DOCK3) and Sirtuin 3 (SIRT3) and mitigated mitochondrial and synaptic dysfunction within the hippocampus of PS-MPs-exposed mice. E4A also diminished the activation of the TLR4-NF-κB-NLRP3 signaling pathway, consequently reducing neuroinflammation. In vitro experiments demonstrated that E4A partially alleviated PS-MPs-induced hippocampal neuronal injury and its effects on microglial inflammation. In conclusion, the findings of this study indicate that targeted activation of ErbB4 receptor may mitigate neuronal damage and subsequent neuroinflammation, thereby alleviating hippocampal neuronal injury induced by PS-MPs exposure and ameliorating cognitive dysfunction. These results offer valuable insights for the development of potential therapeutic strategies.
Insights
Targeted activation of the epidermal growth factor receptor 4 (ErbB4) using E4A reduced cognitive deficits in mice exposed to polystyrene microplastics (PS-MPs). This approach also decreased neuroinflammation and neuronal damage, offering potential therapeutic strategies.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Polystyrene microplastics (PS-MPs) impact the nervous system.
- Epidermal growth factor receptor 4 (ErbB4) activation is key in neuronal injury and regeneration.
Purpose of the Study:
- Investigate if targeted ErbB4 activation can mitigate PS-MPs-induced neuronal injury.
- Evaluate the therapeutic potential of E4A, an ErbB4 agonist.
Main Methods:
- Administered E4A to mice exposed to PS-MPs.
- Assessed cognitive function, hippocampal neuronal health, and molecular markers.
- Conducted in vitro experiments on hippocampal neurons and microglia.
Main Results:
- E4A significantly improved cognitive behavior in PS-MPs-exposed mice.
- E4A upregulated DOCK3 and SIRT3, mitigating mitochondrial and synaptic dysfunction.
- E4A reduced neuroinflammation by inhibiting the TLR4-NF-κB-NLRP3 pathway.
- E4A partially alleviated PS-MPs-induced neuronal injury and microglial inflammation in vitro.
Conclusions:
- Targeted ErbB4 activation with E4A shows promise in mitigating PS-MPs-induced neurotoxicity.
- This strategy may offer a therapeutic approach for cognitive dysfunction and neuroinflammation caused by microplastic exposure.
