Silica Nanoparticles Disclose a Detailed Neurodegeneration Profile throughout the Life Span of a Model Organism.

The incidence of age-related neurodegenerative diseases is rising globally. However, the temporal sequence of neurodegeneration throughout adult life is poorly understood. To identify the starting points and schedule of neurodegenerative events, serotonergic and dopaminergic neurons were monitored in the model organism C. elegans, which has a life span of 2-3 weeks. Neural morphology was examined from young to old nematodes that were exposed to silica nanoparticles. Young nematodes showed phenotypes such as dendritic beading of serotonergic and dopaminergic neurons that are normally not seen until late life. During aging, neurodegeneration spreads from specifically susceptible ADF and PDE neurons in young C. elegans to other more resilient neurons, such as dopaminergic CEP in middle-aged worms. Investigation of neurodegenerative hallmarks and animal behavior revealed a temporal correlation with the acceleration of neuromuscular defects, such as internal hatch in 2-day-old C. elegans. Transcriptomics and proteomics of young worms exposed to nano silica showed a change in gene expression concerning the gene ontology groups serotonergic and dopaminergic signaling as well as neuropeptide signaling. Consistent with this, reporter strains for nlp-3, nlp-14 and nlp-21 confirmed premature degeneration of the serotonergic neuron HSN and other neurons in young C. elegans. The results identify young nematodes as a vulnerable age group for nano silica-induced neural defects with a significantly reduced health span. Neurodegeneration of specific neurons impairs signaling by classical neurotransmitters as well as neuropeptides and compromises related neuromuscular behaviors in critical phases of life, such as the reproductive phase.

A Multisystemic Approach Revealed Aminated Polystyrene Nanoparticles-Induced Neurotoxicity.

Exposure to plastic nanoparticles has dramatically increased in the last 50 years, and there is evidence that plastic nanoparticles can be absorbed by organisms and cross the blood-brain-barrier (BBB). However, their toxic effects, especially on the nervous system, have not yet been extensively investigated, and most of the knowledge is based on studies using different conditions and systems, thus hard to compare. In this work, physicochemical properties of non-modified polystyrene (PS) and amine-functionalized PS (PS-NH2 ) nanoparticles are initially characterized. Advantage of a multisystemic approach is then taken to compare plastic nanoparticles effects in vitro, through cytotoxic readouts in mammalian cell culture, and in vivo, through behavioral readouts in the nematode Caenorhabditis elegans (C. elegans), a powerful 3R-complying model organism for toxicology studies. In vitro experiments in neuroblastoma cells indicate a specific cytotoxic effect of PS-NH2 particles, including a decreased neuronal differentiation and an increased Amyloid ß (Aß) secretion, a sensitive readout correlating with Alzheimer's disease pathology. In parallel, only in vivo treatments with PS-NH2 particles affect C. elegans development, decrease lifespan, and reveal higher sensitivity of animals expressing human Aß compared to wild-type animals. In summary, the multisystemic approach discloses a neurotoxic effect induced by aminated polystyrene nanoparticles.

Tire components, age and temperature accelerate neurodegeneration in C. elegans models of Alzheimer's and Parkinson's disease.

Increasingly, traffic-related air pollution is linked with Alzheimer's disease, Parkinson's disease and other neurodegenerative conditions. The molecular pathways underlying the epidemiologic observations are unknown. In this study, models of neurodegenerative disorders in the nematode Caenorhabditis elegans were used to investigate effects of the tire wear component nano silica. Life span-resolved exposition of reporter strain GRU102 that expresses the Alzheimer's peptide amyloid beta1-42 with silica nanoparticles significantly reduced locomotory fitness in middle-aged nematodes. A specific vulnerability of 10-day-old nematodes was identified in GRU102 cultivated at ambient temperatures of 15 and 20 °C. Reduction of locomotory fitness was corroborated in the Parkinson's disease model BZ555. Nano silica from different sources, including genuine tire components, accelerated the neurodegeneration of dopaminergic neurons in BZ555 nematodes. Dendritic beading was observed in single PDE neurons along the lateral side of the posterior body. In both, the Alzheimer's disease model GRU102 and the Parkinson's disease model BZ555 increased age and the non-chemical exposome factor temperature aggravated nano silica-induced neurodegeneration. Middle-aged cohorts were defined as the most vulnerable age-group. The results suggest C. elegans disease models as a platform to elucidate the relationships between neurodegeneration, age and the environmental factor ambient temperature after exposition with defined components of non-exhaust emissions or sampled urban aerosols.

Pollutants corrupt resilience pathways of aging in the nematode C. elegans.

Delaying aging while prolonging health and lifespan is a major goal in aging research. One promising strategy is to focus on reducing negative interventions such as pollution and their accelerating effect on age-related degeneration and disease. Here, we used the short-lived model organism C. elegans to analyze whether two candidate pollutants corrupt general aging pathways. We show that the emergent pollutant silica nanoparticles (NPs) and the classic xenobiotic inorganic mercury reduce lifespan and cause a premature protein aggregation phenotype. Comparative mass spectrometry revealed that increased insolubility of proteins with important functions in proteostasis is a shared phenotype of intrinsic- and pollution-induced aging supporting the hypothesis that proteostasis is a central resilience pathway controlling lifespan and aging. The presented data demonstrate that pollutants corrupt intrinsic aging pathways. Reducing pollution is, therefore, an important step to increasing healthy aging and prolonging life expectancies on a population level in humans and animals.