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
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.
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.
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.
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.