Polystyrene nanoplastic exposure exacerbates epileptic vulnerability in SCN1A mutation models

07/11/2026

AI Summary

50 nm polystyrene nanoplastics penetrated SCN1A+/- organoids deeper than 100 nm and induced stronger inflammation, apoptosis, and DNA fragmentation at equal mass.
PS-NP exposure disrupted steroid homeostasis with genotype-dependent cortisol elevations and perturbed neurotransmission via reduced GABA and glutamate, decreased GAD2, increased VGLUT2.
Exposed Scn1a+/- mice showed hyperactivity and faster progression to Racine stages 3-5 under thermal induction; 11β-HSD1 inhibition reversed hyperactivity but not seizure threshold.

TL;DR (AI Generated)

Here, we examined whether polystyrene nanoplastic (PS-NP) exposure alters seizure susceptibility in SCN1A+/- cerebral organoids and Scn1a+/- mice, modeling the severe genetic epilepsy Dravet syndrome.

Exposure disrupted steroid homeostasis-causing genotype-dependent cortisol elevations-and perturbed neurotransmitter systems in SCN1A-deficient models via reduced GABA and glutamate, accompanied by decreased GAD2 and increased VGLUT2 expression.

In vivo, exposed Scn1a+/- mice exhibited hyperactivity and reached Racine stages 3-5 more rapidly under thermal induction, demonstrating a reduced seizure threshold.

Basic summary

J Hazard Mater. 2026 Nov 3;518:144105. doi: 10.1016/j.jhazmat.2026.144105. Online ahead of print.

ABSTRACT

Micro- and nanoplastics are pervasive contaminants detected in human tissues that cross the blood-brain barrier to induce neuroinflammation, apoptosis, and neurotoxicity. Here, we examined whether polystyrene nanoplastic (PS-NP) exposure alters seizure susceptibility in SCN1A^+/- cerebral organoids and Scn1a^+/- mice, modeling the severe genetic epilepsy Dravet syndrome. At equal mass concentrations, 50 nm PS-NPs penetrated organoids more deeply and upregulated inflammatory and neurotoxic gene expression more robustly than 100 nm particles, inducing apoptotic activation and significant DNA fragmentation. Exposure disrupted steroid homeostasis-causing genotype-dependent cortisol elevations-and perturbed neurotransmitter systems in SCN1A-deficient models via reduced GABA and glutamate, accompanied by decreased GAD2 and increased VGLUT2 expression. In vivo, exposed Scn1a^+/- mice exhibited hyperactivity and reached Racine stages 3-5 more rapidly under thermal induction, demonstrating a reduced seizure threshold. Pharmacological inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversed this hyperactivity but failed to restore the seizure threshold. Together, these findings indicate that PS-NP exposure exacerbates seizure vulnerability in genetically susceptible backgrounds, accompanied by marked neurochemical, endocrine, and apoptotic disruptions. These results support a ‘second-hit’ model wherein environmental nanoplastics act as external triggers in genetic epilepsy, underscoring the vital need to incorporate gene-environment interactions into neurotoxicological risk assessments.

PMID:42994359 | DOI:10.1016/j.jhazmat.2026.144105

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