Evaluating the effects of air pollution derived toxic nanoparticles on astrocyte reactivity and neurodegeneration

Villani, Beatrice

Abstract

Particulate Matter is a toxicologically relevant air pollution component that has been shown to damage the cardiopulmonary system. Emission of ultrafine particulate matter – the most toxic type – is not regulated around the globe. Recent evidence from epidemiological studies, supported by a recent UK government COMEAP advisory report, states that exposure to these particles increases risk of dementia and cognitive decline. However, the variability in the design of public health studies, so-far, prevents confirmation of a causal link between specific types of air pollution associated particles and neurodegeneration, and few empirical analyses have assessed the effects of specific particles on brain derived cells. This research aimed to investigate the effects of ultrafine carbon black (UFCB), a surrogate air pollution derived nanoparticle, on primary cortical astrocyte reactivity and potential for subsequent neurotoxic or neuroprotective functions. Viability of primary human cortical astrocytes was measured, using the WST-1 assay, following exposure across a toxicologically relevant UFCB nanoparticle concentration range. qRT-PCR was used to investigate astrocyte reactivity, by via GFAP expression, and polarisation, by measuring expression of astrocyte genes linked to neurotoxic A1 (LCN2 and GBP2) or neuroprotective A2 (S100A10) states. Although not statistically significant, a trend to increased S100A10 expression, but no change in GBP2 or LCN2, was observed after UFCB exposure. Attempts were also made to measure levels of the astrocyte-specific pro-inflammatory marker LCN2 and the anti-inflammatory marker IL-6 in response to lethal and sub-lethal doses of UFCB. Lcn2 levels were below the limit of detection, but low levels of IL6 were measured in astrocyte conditioned media and were mainly unchanged by UFCB exposure. To further investigate the effects of UFCB exposure on neuronal toxicity, differentiated NT2 neuronal-like cells were treated with either UFCB-stimulated astrocyte conditioned media or direct UFCB and viability measured. Direct exposure to lethal and sub-lethal UFCB doses resulted to be toxic to differentiated NT2 neuronal-like cells, whereas conditioned media lead to negligible effects. These preliminary results indicate that acute exposure to UFCB leads to astrocytes adopting a more neuroprotective role and morphology, and that any toxic neuro-inflammatory responses to UFCB are not clearly astrocyte-mediated. Further research is required to confirm these findings.

• Thesis Type: Thesis
• Deposit Date: Aug 21, 2023
• Publicly Available Date: Aug 21, 2023
• DOI: https://doi.org/10.17869/enu.2023.3175435
• Award Date: Jul 5, 2023