Let’s play a game. Wherever you are, without turning around or changing your field of vision, count how many plastic objects you see. In my small 50 m² apartment, I count 46. This little exercise gives you a glimpse of how plastics have contributed to advancing modern technology and society, thanks to their affordability, durability, and versatility. However, the widespread use of these materials also contributes to pollution, including the formation of microplastics.

What are microplastics, and why should we be concerned about them?

What are microplastics?  

Microplastics are tiny particles smaller than 5 mm (about the length of a grain of rice), generated by physical wear and tear or when plastics interact with environmental factors like sunlight and air. Because plastic takes a long time to break down and can persist for many years, microplastics accumulate in both terrestrial and aquatic ecosystems, posing a threat to both the environment and human health.

We are exposed to microplastics through various sources, including water, seafood, and everyday items like clothing, toothpaste, and things stored in plastic containers. In 2020, a study estimated that, on average, an adult man in the U.S. consumes 312 particles of microplastics daily and 114.000 annually through food and water, while an adult woman consumes and inhales slightly less, 258 particles daily and 94.000 annually.  This exposure, equivalent to around the size of an Eiffel Tower in a lifetime according to another study, can adversely affect cell health and metabolism. That’s why researchers are focused on studying and reducing the spread and harmful impacts of microplastics.

While, in the past, studies predominantly focused on microplastics in marine environments – as ocean pollution is the most visible outcome of microplastics – researchers are now emphasising understanding their effects on mammals, especially humans. To date, this shift in emphasis has only resulted in a limited amount of evidence on the impact of microplastics on humans. Closing the gaps in our knowledge requires more in-depth research on mammals, specifically investigating the complex connections between microplastics and human health.

New perspectives on interactions between microplastics and mammals

In this knowledge desert, Professor Jaime Ross of the University of Rhode Island and her team stand out like a new sprout. Jaime Ross’s multidisciplinary research team aims to understand how the widespread infiltration of microplastics can affect the brain’s abilities, specifically how it can lead to neurological disorders and diseases, such as Alzheimer’s.

Because we know so little about the influence of microplastics on mammals, Ross’s team wanted to explore the potential impact of microplastic exposure on mammalian physiology and cognitive abilities. They conducted the study in a mouse model, which is standard practice in the study of human disorders because they have brain structures similar to ours, but due to their shorter life span, abnormalities arise faster.

The research team exposed mice of both young (4-month-old) and old (21-month-old) age groups to diverse doses of microplastics, specifically polystyrene particles. This exposure was administered by diluting the microplastics in their drinking water over a three-week period. Following this exposure, the mice underwent behavioural tests, and the team investigated the accumulation of microplastics in various tissues. To precisely identify the sites of microplastic accumulation within different tissues, the researchers utilized red fluorescent microplastic particles.

So, let’s follow the journey of these particles inside the hum… um, well, the rodent body.

Physiological Consequences

Following a three-week exposure, Ross’s team euthanised and dissected mice from both groups to identify which tissues the red fluorescent microplastics had accumulated in. In particular, the researchers focused on examining the gastrointestinal tract, liver, kidney, spleen, heart, lungs, and brain.

Because the microparticles were orally administered through drinking water, Ross’s team thought they would likely be detected in tissues involved in digestion and detoxing, such as the gastrointestinal tract, liver, and kidneys. However, they also found microplastics in other tissues, such as the heart and lungs, which suggests that microplastics can bypass the digestive system and enter the cardiocirculatory system and even the brain. This latter discovery is especially important because it demonstrates that microplastics can cross the blood-brain barrier – a physiological barrier that protects the brain from potentially harmful or toxic substances circulating in the blood. And that is not good news. The fact that microparticles can enter the brain could be a significant concern since the brain is often considered one of the most (if not the most) crucial and sensitive organs, and Ross’s team is well aware of that.

But wait a moment! How is it possible for microplastics to cross the blood-brain barrier? Well, we don’t know for sure – the scientific world often revolves around “maybes”. Several studies (such as Zaki et al. and Claeys et al.) have suggested that the ability of a toxin to reach the brain may be partly due to liver dysfunction. Since this organ is a major site of blood detoxification, if the liver doesn’t function properly, toxins can accumulate in the blood and ultimately reach the organs, including the brain.

To determine if liver dysfunction could explain how microplastics reach the brain, Ross’s team analysed immune markers – measurable substances commonly used as indicators of inflammation, the smoke that might tell you where a fire is – in the livers of both the young and old mice. They found an increase in these markers in both groups of mice compared to the controls (mice included in this study but not subjected to microplastic exposure).  This means that exposure to microplastics could introduce liver inflammation and dysfunction, which could lead to a lack of blood detoxification. This lack of blood detoxification could lead to microparticles such as microplastics staying in the bloodstream long enough to reach the brain.

Fearing that microparticles could also trigger inflammation in the central nervous system, Ross and her team studied Glial Fibrillary Acidic Protein (GFAP), a protein commonly used as an indicator for inflammation in brain tissue. Ross’s team expected to observe an increase in this marker because the increase in GFAP expression is typically linked to heightened neuroinflammation, and they reasoned the accumulation of microplastics would likely cause inflammation. However, the analysis revealed an unexpected outcome: mice exposed to microplastics had lower GFAP levels compared to mice that hadn’t been exposed. Surprisingly, results indicated a lack of inflammatory response in the brain.  

Although the absence of an inflammatory response in this study does not rule it out entirely, as GFAP is just one of the molecules involved in the inflammatory response in the brain, an interesting question remained: Why do GFAP levels in mice exposed to microplastics decrease? To try to answer this question, researchers needed to change their approach, change their perspective.

Behavioural Consequences: The Keystone?

After the three-week exposure to microplastics – on top of looking for accumulation in tissues – the same mice underwent a series of behavioural tests. Interestingly, young and old mice exposed to microplastics began to move and behave strangely, exhibiting behaviours akin to dementia in humans. Overall, all tests showed significant variations in behavioural parameters – such as distance travelled – between the control and exposed groups, but variations seemed to be more pronounced in older animals, possibly due to age-related deterioration worsening the effects of microplastics on behavioural performance. However, the behavioural changes observed in young mice suggest that even without considering age, microplastics can induce altered behaviour in rodents after just three weeks of exposure.

According to the authors, these abnormal behaviours may be related to the decrease in GFAP mentioned previously. Previous studies (such as Olabarria et al. and Verkhratsky et al.) have suggested that GFAP expression might decrease in the early stages of certain neurological conditions, such as Alzheimer’s, or in younger patients with disorders like major depressive disorder.

However, GFAP is not the sole defining factor in such a complex condition, and the rodent model is not a perfect parallel to the human body. This study contributes just one piece to the puzzle of our understanding of how microplastics affect neurological conditions in humans.

Key Takeaways

This study contributes to our limited knowledge regarding the consequences of microplastic exposure on mammalian – and, hence, human – health. The research team led by Jaime Ross has highlighted a decrease in GFAP – often associated with the early stages of neurodegenerative diseases such as Alzheimer’s – and abnormal behaviour in young and old mice exposed to various doses of microplastics for three weeks.

However, this study is only the beginning. How do the duration and type of exposure (through the air, ingestion, etc.) affect the negative consequences for our bodies? Are some plastics more toxic than others? These are just two of the many questions we need to ask to understand the effects of these substances, which are indeed useful for technological and social progress but come with harms that should not be underestimated.

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Ross’s team includes Research Assistant Professor Giuseppe Coppotelli, graduate student Lauren Gaspar in Biomedical and Pharmaceutical Sciences, and graduate student Sydney Bartman in the Interdisciplinary Neuroscience Program.

references

1. Gaspar, L.; Bartman, S.; Coppotelli, G.; Ross, J.M. Acute Exposure to Microplastics Induced Changes in Behavior and Inflammation in Young and Old Mice. Int. J. Mol. Sci. 2023, 24, 12308.
2. Zeynep Akdogan, Basak Guven, Microplastics in the environment: A critical review of current understanding and identification of future research needs, Environmental Pollution, Volume 254, Part A, 2019, 113011, ISSN 0269-7491.
3. Zaki, A.E.O.; Ede, R.J.; Davis, M.; Williams, R. Experimental Studies of Blood Brain Barrier Permeability in Acute Hepatic Failure. Hepatology 1984, 4, 359–363.
4. Claeys, W.; Van Hoecke, L.; Lefere, S.; Geerts, A.; Verhelst, X.; Van Vlierberghe, H.; Degroote, H.; Devisscher, L.; Vandenbroucke, R.E.; Van Steenkiste, C. The neurogliovascular unit in hepatic encephalopathy. JHEP Rep. 2021, 3, 100352.
5. Olabarria, M.; Noristani, H.N.; Verkhratsky, A.; Rodríguez, J.J. Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer’s disease mouse model: Mechanism for deficient glutamatergic transmission? Mol. Neurodegener. 2011, 6, 55.
6. Verkhratsky, A.; Rodrigues, J.J.; Pivoriunas, A.; Zorec, R.; Semyanov, A. Astroglial atrophy in Alzheimer’s disease. Pflüg. Arch. Eur. J. Physiol. 2019, 471, 1247–1261.