Life span-resolved nanotoxicology: neuronal targets and vulnerable age-groups in the nematode Caenorhabditis elegans

• Applicant: Professorin Dr. Anna von Mikecz
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 435335313

Continuously growing applications of engineered nanomaterials, their inevitable distribution into the environment as well as increasing application as food additives calls for the investigation of relevant exposition scenarios. Thus, the submitted grant proposal suggests long-term analyses, e.g. whole-life nanotoxicology in the nematode roundworm Caenorhabditis elegans.Our preliminary work shows that the nervous system of the nematode represents a sensitive target organ of adverse effects of nanomaterials. Nano silica induce global amyloid protein aggregation that also affects serotonergic neurons. Specific neurons degenerate and serotonergic neurotransmission is impaired which in turn promotes defects of neuromuscular behavior such as egg-laying and forward locomotion. Since these defects otherwise occur in aged adult C. elegans we hypothesize that the toxicity of certain nanomaterials manifests in a reduced health span of the worms due to amyloid protein aggregation and degeneration of decisive neurons.Thus, the project proposal suggests whole-life investigation of the temporal interactions between the observed neurodegeneration and neural behavior defects. Accordingly, reporter worms of serotonergic, dopaminergic and GABAergic neurons are characterized concerning the chronological sequence and patterns of nanoparticle-induced neurodegeneration. In parallel, defects of behavioral phenotypes will be quantified that are controlled by the respective (degenerated) neurons. Whole-life analyses enable the identification of age-groups that are especially sensitive, e.g. vulnerable, to certain nanomaterials. The vulnerable age-groups will be interrogated for defects of protein homeostasis and increased amyloid protein aggregation. The scheduled life span-resolved characterization of interactions between protein aggregation, neurodegeneration, neural fitness and reduced health span will narrow down biological effects in C. elegans that are useful to develop a cost-effective and reliable screening platform for different nanomaterials. Moreover, the concept of life span-resolved studies might not only innovate nanotoxicology, but investigations of pollutants and their combinations in general.By investigation of the nanotoxicity in aging C. elegans the submitted grant proposal aims to identify nanoparticles that do not promote defects of the neural system and thereby maintain a maximal health span ('eurosafe nanomaterials'.

• DFG Programme: Research Grants