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In vitro neurotoxicity of transport-derived (ultra)fine particles (TUBE)

 

 
Principle investigator: Lora Gerber, M.Sc 
Project leaders:
Remco Westerink, Ph.D.
Flemming Cassee, Ph.D.

 

Project description:
 
The overall aim of TUBE (Transport derived Ultrafines and the Brain Effects) is to gain insights on the effects of traffic related ultrafine particles (UFPs) beyond the lung on brain health. Our major tasks within TUBE include the identification of UFPs with neurotoxic potency and the investigation of the impact of primary cytotoxic and inflammatory effects at the port of entry (lung) induced by UFPs on neuronal development, function and degeneration. We aim to understand the biological processes and to discover the underlying mechanisms leading to neurotoxic effects of air pollutants by UFPs. Moreover we are improving, promoting and combining the application of in vitro models contributing to the principle of the 3R’s and providing an in vitro risk assessment approach of inhaled UFPs with regard to human brain health.
 
Methods:
Collected samples of traffic related particles derived from several cities all over Europe are screened in primary cortical rat cultures for their impact on neuronal development, function and degeneration using muliwell MicroElectrode Arrays (mwMEA). The effects of UFPs will be assessed through direct exposure of the culture or following permeation through human lung cells in an air-liquid interface (ALI) system. The latter provides an integrated in vitro model for a more advanced simulation of the human body. Additionally, to characterize the impact of traffic related ultrafine particles on neurodegeneration iPSC-derived cells of familial and sporadic Alzheimer’s diseases patients will be used in the final stages of the project.
 
 
Background:

The exposure to traffic derived ultrafine particles (UFPs) does not only constitute a risk to the lung, but also to extrapulmonary target organs such as the brain. Due to their extreme small size (< 100 nm in diameter), UFPs can translocate through epithelial barriers and finally reach the brain. The brain is among the most vulnerable organs in the human body and very little is known about whether and how traffic-derived UFPs affect brain development and health. In recent years, evidence showing effects on the brain is increasing and neurological diseases, including Alzheimer´s disease have been associated with living near heavy traffic. However, so far only particles larger than 23 nm have been included in (regulatory) guidelines and hazard characterization and risk assessment, whereas a large fraction of UFPs has a size smaller than 23 nm.

Due to this discrepancy the aim of TUBE is to study the relative impact of UFPs in the pollutant mixture that is generated by combustion engines beyond the lung on brain health. The TUBE project aims on revealing the mechanisms and exposures both behind cardiorespiratory diseases and beyond the current knowledge in neurological diseases. This research is part of the EU-funded TUBE project.
 
Recent publications:
- Will follow soon.