Mobiele menu

neurotoxic effects of small plastic particles

Projectomschrijving

Aanleiding

De mens wordt op dagelijkse basis blootgesteld aan micro- en nanoplastics (MNPs) via voedsel, (drink)water en consumentenproducten. Maar het is onduidelijk of deze plastic deeltjes negatieve effecten hebben op onze gezondheid. Ondanks de bescherming door de bloed-hersenbarrière, zijn de hersenen bijvoorbeeld kwetsbaar voor effecten van metaal nanodeeltjes. Wellicht geldt hetzelfde voor MNPs.

Doel en onderzoeksopzet

In dit project is onderzocht of en in welke mate MNPs in de hersenen terecht kunnen komen. Dit is onderzocht door gebruik te maken van een in vitro model voor de bloed-hersenbarrière. Ook is onderzocht of MNPs nadelige effecten hebben op de ontwikkeling en/of het functioneren van de hersenen in vitro.

Resultaten

Zowel microplastics als nanoplastics kunnen de bloed-hersenbarrière passeren en de hersenen bereiken. Ook laten de data zien dat MNPs het enzym acetylcholine-esterase, wat een belangrijke rol speelt bij communicatie tussen hersencellen, kunnen remmen. De metingen met gekweekte hersencellen laten echter zien dat de effecten van MNPs op de ontwikkeling en het functioneren van de hersenen beperkt zijn. Deze bevindingen pleiten voor vervolgonderzoek naar de langetermijneffecten van MNPs op immuuncellen in de hersenen (neuroinflammatie) en de indirecte gevolgen daarvan, met name in menselijke hersencellen.

Uitvoerende partijen

Dit project is uitgevoerd door Dr. R.H.S. Westerink (Universiteit Utrecht) in nauwe samenwerking met Université d’Artois (Frankrijk) en Deltares.

Verslagen


Eindverslag

  

  

Samenvatting van de aanvraag

Humans are exposed to different micro- and nanoplastics (M-NPs) on a daily basis via the food chain, (drinking) water and consumer products. It is more than likely that these M-NPs to some extent reach the systemic circulation as it has been shown that engineered M-NPs, analogous to metal and traffic-related nanoparticles, are subject to uptake in different species of fish. Yet, it is unclear if exposure to these plastic particles has any adverse effects on human health. The brain is among the most vulnerable organs in the human body and is targeted by many toxicants. While the brain is protected from chemical exposures by the blood-brain-barrier (a highly selective, semi-permeable tight layer of endothelial cells and pericytes surrounding brain capillaries), many chemicals and particles can bypass or permeate this barrier. Increasing evidence demonstrates that nanoparticles, including metal and traffic-related particles, do actually reach the brain. Exposure to such nanoparticles has been linked to detrimental effects on the aging brain, including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Similarly, exposure to ultrafine particles during brain development has been shown to result in neurodevelopmental disorders, including autism. Given the vulnerability of the brain and the burden of neurodevelopmental and neurodegenerative disorders, circulating M-NPs may pose a huge threat to human health. This proposal will therefore investigate if and to what extent M-NPs can reach the brain using a human in vitro cell model for the blood-brain-barrier (BBB). Human brain-like endothelial cells cultured on a Transwell™ system will be exposed to differently sized plastic reference particles as well as mixtures of environmentally relevant M-NPs with diverse chemical composition. Effects of M-NPs on BBB cell viability and permeability will be assessed following 4h and 24h exposure. In parallel, medium will be collected for microscopy analyses to determine which M-NPs permeate the BBB model, and to what extent. Additionally, this proposal will investigate if plastic particles have any adverse effects on brain function and brain development in vitro. To that end, the M-NP-containing effluent medium from the BBB model will be used for exposure of rat primary cortical cultures. Rat primary cortical cultures develop into spontaneously active neuronal networks that are suitable for assessing functional neurotoxicity from chemical exposure using microelectrode arrays (MEAs). Rat primary cortical cultures grown on MEAs will be exposed for 1h to the effluents from the BBB to investigate acute neurotoxic effects (on neuronal activity and viability). In subsequent recordings, effects of prolonged, developmental exposures (14 days) will be investigated to reveal whether M-NPs can affect neurodevelopment. As certain nanomaterials are known to bypass the BBB and the BBB is not yet functional during early brain development, we will also expose rat primary cortical cultures directly (1h – 14 days) to the different reference and environmentally relevant M-NPs to assess acute and developmental neurotoxicity in the absence of the BBB. Next, those conditions that show most pronounced effects will also be tested using human iPSC-derived neurons to increase translatability to human brain development and function. Overall, this proposal will identify the potential of plastic particles to induce neurotoxicity in relation to size, chemical composition and ability to reach the brain. As such, our results will be an essential proof of principle that urges further research into M-NPs of different sizes and chemical composition. Confirmation of the neurotoxic potential would plead for serious mitigation strategies to prevent exposure and the potentially associated burden of disease.

Kenmerken

Projectnummer:
458001002
Looptijd: 100%
Looptijd: 100 %
2019
2020
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. R.H.S. Westerink
Verantwoordelijke organisatie:
Universiteit Utrecht

Contact

Wilt u meer informatie over dit project? Neem contact op via onderstaande contactgegevens.

Frank Pierik

Programmamanager
MicroplasticsHealth [at] zonmw.nl

Marije van der Kamp

Programmasecretaris
MicroplasticsHealth [at] zonmw.nl