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Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Adverse interactions of plastic nanoparticles with cultured primary microglial cells
Kamil Adamiak1, Lidia Struzynska2
1Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawińskiego str., Warsaw 02-106, Poland; Doctoral School of Translational Medicine, Centre of Postgraduate Medical Education, 99/103 Marymoncka str., Warsaw 01-813, Poland.
Abstract:
Due to ever-increasing production, plastics have become ubiquitous in the environment, with polystyrene (PS) being one of the most commonly produced types of plastics. Under the influence of mechanical pressure or UV radiation, plastic waste can decompose into smaller micro/nanoparticles (MPs/NPs), posing a threat to biological life, including humans. Recent findings indicate that MPs/NPs can penetrate biological barriers, including the blood-brain barrier (BBB) and affect cells of the central nervous system (CNS), including microglia, immune cells that play a key role in monitoring the neuronal microenvironment and responding to toxic compounds. The results of our study using primary microglial cells show that exposure to different concentrations (1, 25, 50 µg/mL) of polystyrene nanoparticles (PS-NPs; 25 nm) for different periods of time (24-48 h) results in a time- and concentration-dependent profile of NP internalization via an actin-dependent pathway. Once absorbed by cells, PS-NPs are directed to the endosomal-lysosomal system and induce cell activation, as evidenced by morphological changes (Sholl parameters) and increased levels of the Iba1 marker. The toxic effect of PS-NPs on primary microglia is expressed by reduced cell viability, overproduction of ROS and increased number of protein carbonyl groups induced by oxidative stress. These changes are accompanied by overexpression of pro-inflammatory chemokines, indicating activation of primary microglial cells towards a pro-inflammatory phenotype. The results suggest that PS-NPs may be a significant environmental risk factor leading to pro-inflammatory activation of microglia, which constitutes the first line of defense in the brain and is associated with the course of many neurological disorders.

