Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway

Area of Science:

• Environmental Science
• Neuroscience
• Toxicology

Background:

• Environmental hazardous substances pose risks to neurological health.
• Polystyrene microplastics (PS-MPs) are prevalent and exhibit neurotoxicity.
• Mechanisms linking PS-MPs to anxiety and neuroinflammation are not fully understood.

Purpose of the Study:

• To investigate the association between PS-MPs and anxiety-like behaviors.
• To elucidate the molecular mechanisms and key proteins involved in PS-MP neurotoxicity.
• To explore the role of microglia activation and inflammation in PS-MP-induced anxiety.

Main Methods:

• Characterization of PS-MPs and assessment of their brain accumulation in mice.
• Behavioral tests to evaluate anxiety-like behavior.
• Proteomics analysis and molecular investigations in BV2 microglia cells.
• Assessment of microglia activation, inflammatory responses, and key protein pathways (NF-κB, HRAS, PERK).

Main Results:

• PS-MPs accumulate in the brain, inducing anxiety-like behavior in mice.
• PS-MP exposure activates microglia and triggers a pro-inflammatory response.
• PS-MPs activate the NF-κB pathway in microglia, upregulating TNFα and IL-1β.
• HRAS is identified as a key factor; its knockdown inhibits PS-MP-induced PERK-NF-κB activation and inflammation.

Conclusions:

• PS-MPs induce anxiety in mice through the HRAS-derived PERK-NF-κB pathway in microglia.
• This pathway activation leads to neuroinflammation and contributes to anxiety-like behaviors.
• Findings provide insights into microplastic neurotoxicity and potential strategies for prevention.