Prolonged developmental TiO₂ nanoparticle exposure at environmentally relevant level drives Parkinson's disease-related phenotypes in Caenorhabditis elegans.

Abstract

Titanium dioxide nanoparticles (TiO₂-NPs) are widely used in consumer and industrial products and are increasingly released into aquatic environments, raising concerns about their potential health risks. The nematode Caenorhabditis elegans has emerged as a valuable bioindicator of water pollution and a practical toxicological tool for water quality monitoring. Here, we investigated the effects of prolonged developmental TiO₂-NP exposure on the development of Parkinson's disease (PD)-related phenotypes in C. elegans and explored the underlying mechanisms. Two transgenic strains were used: BZ555, which expresses green fluorescent protein in dopaminergic neurons, and NL5901, which constitutively expresses human α-synuclein (α-syn) in muscle. Prolonged developmental exposure to 0.1 µg/mL TiO₂-NPs, a concentration comparable to the upper range of previously reported TiO₂ engineered-particle concentrations in surface waters, 1 and 10 µg/mL TiO₂-NPs increased α-synuclein-associated fluorescence in NL5901 worms, and induced dopaminergic neuronal abnormalities in BZ555 worms. TiO₂-NPs (1 and 10 µg/mL) also elevated a whole-worm oxidative signal in BZ555 worms. The dopaminergic neuronal abnormalities observed after 84 h developmental exposure and the impaired basal slowing behavior observed under a separate 24 h exposure paradigm (1 and 10 µg/mL) provide complementary evidence that TiO₂-NPs can disrupt dopaminergic function. Moreover, mechanistic analysis revealed that TiO₂-NPs at 1 µg/mL upregulated skn-1, gst-38, and gcs-1, key regulators of the antioxidant defense system, following TiO₂-NP exposure. Taken together, these results demonstrate that prolonged developmental TiO₂-NP exposure induces dopaminergic neuronal abnormalities, increased α-synuclein-associated fluorescence, and behavioral abnormalities in C. elegans, potentially with involvement of a protective SKN-1-associated antioxidant response. Our findings identify environmentally relevant level of TiO₂-NP exposure as a potential risk factor for PD-related phenotypes and highlight the need to evaluate nanoparticle neurotoxicity in aquatic exposure contexts.

Abstract as supplied by the indexing source. © the authors / publisher.