The Effect of Micro-Nano-Plastics Accumulation on Waste Removal from the CNS via Cerebrospinal Fluid Transport

University Of New Mexico Health Scis Ctr, Albuquerque NM

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Abstract

The exponential rise in plastic production has resulted in plastics dominating the Anthropocene era. Micro-nano-plastics MNPs infiltrate the ecosystem, contaminate the food chain, and contradict the United Nations' Sustainable Development Goals, posing a significant threat to public health. It is essential to comprehend the possible health hazards of inhaling or consuming MNPs. Toxicological assessments of plastic pollution may differ from those of earlier chemical contaminants because of the complex uptake and simultaneous exposure to particles with diverse physicochemical properties and polymers. Studying human exposure can improve toxicology and expand our understanding of bioaccumulated polymeric materials. Our team has successfully developed and validated a precise method for quantifying the concentration of MNPs in human tissues. Our observations reveal that MNPs have an affinity for accumulating in the brain. We have found that plastic accumulation in the brain can exceed 0.5% of the brain's total weight, and this concentration seems to increase with time. These findings raise important questions about the brain's ability to clear waste and its long-term consequences. Glymphatic fluid transport is crucial for clearing waste from the brain. It consists of a network of peri-arterial and peri-venous conduits coupled by aquaporin-4 (AQP4) water channels on glial cells' end feet. CSF enters the glymphatic system through the spaces around arteries, mixes with interstitial fluid, delivers nutrients to neurons, and removes waste proteins. Disruption of CSF circulation can cause harmful substances and proteins to accumulate, leading to neurodegenerative diseases. Our project investigates the presence of MNPs in human CSF to understand their impact on glymphatic clearance in the central nervous system (CNS). Our first aim is to employ cutting-edge microscopy and spectroscopy techniques to comprehensively characterize and quantify MNPs in human CSF. As CSF provides crucial insights into the accumulation of harmful substances and waste products in the brain, our second aim is to explore whether MNPs in the brain affect CSF clearance through the glymphatic system. To achieve our objectives, we will analyze CSF samples for metal levels and specific biomarkers associated with neurodegenerative diseases, including the Aâ42/40 ratio, phosphorylated and total Tau concentration, and AQP4. Through rigorous statistical analysis, we aim to establish correlations between demographic information, MNP concentration, polymer distribution, metal levels, and neurodegenerative biomarkers. This project represents a step towards unraveling the neurotoxic implications of plastic bioaccumulation in the CNS, with a particular emphasis on brain waste clearance. By leveraging interdisciplinary methodologies, we anticipate significant contributions to the field of public health and proactive intervention efforts.