Understanding the impact of nanoplastics on the development of neurological disorders

Project Information

NanoGlia

Grant agreement ID: 851257

DOI

10.3030/851257

Project closed

EC signature date 23 January 2020

Start date 1 April 2020

End date 31 March 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 497 193,00

EU contribution

€ 1 497 193,00

Coordinated by

RHEINISCHE FRIEDRICH-WILHELMS-UNIVERSITAT BONN
Germany

Periodic Reporting for period 3 - NanoGlia (Understanding the impact of nanoplastics on the development of neurological disorders)

Reporting period: 2023-04-01 to 2024-09-30

Summary of the context and overall objectives of the project

An omnipresent but understudied environmental risk for our immune system is pollution by nano-sized plastics. Plastic particles have been detected in a wide variety of ecosystems and have been shown to enter and spread in the food web. Recently, microplastics have been detected in human blood. Ingested nanoplastics can translocate from the gut to the lymph and circulatory systems and have the capacity to cross the blood-brain barrier in mammals. However, the long-term bioavailability and toxicity of nanoplastics in our body is unknown. Macrophages constantly sense and respond to environmental changes as part of their housekeeping and protective functions that are essential for tissue homeostasis and immunity In NanoGlia, we are using rodent animal models to investigate cellular and molecular changes in various tissues, with a focus on the brain, that occur upon ingestion of micro- and nanoplastics. We study whether and how nano- and microplastics crossing the placenta induce developmental reprogramming events in fetal macrophages, thereby influencing organogenesis. Furthermore, we analyse whether nano- and microplastics trigger macrophage activation at postnatal stages and whether this immune activation leads to permanent changes in tissue function. Our holistic approach will reveal ground-breaking mechanistic insights into the environmentally triggered pathogenesis of metabolic and neurological disorders.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have performed acute and chronic treatment with micro- and nanoplastics in adult mice showing that the size determines the path of plastic particles throughout the body. Nanoplastics have the capacity to cross the blood-brain barrier and induce cellular and molecular changes in microglia after three months of chronic plastic treatment. Additionally, we could observe metabolic phenotypes induced by micro- and nanoplastics. After a recovery phase of six months after the chronic treatment, we still could observe plastic particles in the liver and spleen, indicating that plastics entering the body is not washed out with time.
We have set up timed pregnancy in guinea pigs to study the impact of micro- and nanoplastics in the offspring born to mothers that have received chronic treatment with plastic particles. The focus here will be studying neurodevelopment, albeit we will also assess the state of metabolic organs such as the liver, as the data from mice indicate that plastics may influence the metabolism.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

As we observed metabolic changes upon treatment of mice with micro- and nanoplastics, we performed a broad metabolic assessment of different organs. We will continue dissecting the molecular mechanisms, with a focus on the gut and the liver since these are the organs that mainly control the uptake and further distribution of plastics throughout the body. We expect to define the precise routes of micro- and nanoplastics after entering through the gut barrier. Further, we have developed a new mouse model that will allow us to study macrophage ontogeny after the treatment of plastics, indicating whether macrophages that take up plastic particles in various tissues undergo apoptosis or other forms of cell death.

Summary of NanoGlia Aims