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The Hidden Dangers of Lead Exposure

Lead exposure during childhood threatens brain development and health.

Rachel K. Morgan, Anagha Tapaswi, Katelyn M. Polemi, Elizabeth C. Tolrud, Kelly M. Bakulski, Laurie K. Svoboda, Dana C. Dolinoy, Justin A. Colacino

― 6 min read


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LEAD is a nasty little metal that causes big problems for our health, especially in kids. Even after strict laws were put in place in the US to limit lead, many kids are still exposed to it. About 1.8 million children under five have lead in their blood at levels higher than what's considered safe. Even more concerning, around half of all Americans faced unsafe lead levels during their childhood.

Lead can sneak into our lives through various ways. It can be found near factories, in our food, in drinking water, and even in old paint and pipes in older homes. When kids are exposed to lead, especially during critical growth stages-like when they are still in the womb or during their early years-it can affect their brain Development and learning abilities.

How Lead Messes with the Brain

Scientists have mostly studied how lead affects the brain using animal tests that use high levels of lead exposure. These studies often show that high levels of lead can mess with metabolism and create oxidative stress, which is not the same as how most of us experience lead exposure in real life. Many tests have used doses far higher than what most children are exposed to nowadays. Therefore, it's important to look into how even lower amounts of lead that kids might face can affect them.

What We Want to Find Out

We're on a mission to understand how lead exposure affects the developing nervous system, especially at levels that are relevant to the population. In previous studies, we noticed that lead exposure during early development caused changes in brain cell types and how they grow. These changes suggested that lead might mess with how proteins are made and how cells respond to stress.

So, we decided to dig deeper into this issue. We are examining how different levels of lead exposure affect cells in a lab, particularly focusing on how it impacts gene activity during brain cell development. We suspect that different stages of cell growth could lead to different effects from lead exposure.

The Lab Work: How to Grow Neurons and Test for Lead

We used a special type of human brain cell called SH-SY5Y, which can be made to act like nerve cells. In the lab, we treated these cells with different amounts of lead while they were developing into neuron-like cells. We chose specific lead doses based on current standards and historical exposure levels. This way, we could see how lead at different amounts interacts with neurons at different stages of growth.

We started by letting the cells grow without any lead to ensure they were healthy. After a few days, we began exposing them to lead while continuing to monitor their health and growth over the next 18 days.

Collecting Samples and Measuring Gene Activity

Throughout the 18-day period, we collected samples regularly to see how lead affected Gene Expression. This means we were looking at how much of specific genes were being turned on or off as the cells grew and were exposed to lead.

First, we removed the liquid the cells were growing in and then used an enzyme to detach the cells from their dish. After that, we broke the cells open to pull out their RNA, which is responsible for carrying genetic information. The RNA was then tested to see how much of each gene was active.

What We Found About Gene Expression

Our data showed that lead exposure does affect gene expression, and the impacts vary depending on the level of lead and the stage of growth of the cells. Although most significant changes occurred at the highest lead levels, we did see important changes with lower levels too.

For instance, at one point in time, we noticed that the expression of a gene called COL3A1 was reduced with lead exposure. This gene is important for the development and movement of Brain Cells. If it's not working properly, it could cause problems in how the brain develops.

Comparing Exposed Cells to Control Cells

To understand the full effects of lead, we also analyzed the gene expression changes in cells that were not exposed to lead. As these control cells grew, they showed their own set of changes. This helped us see which differences were directly related to lead exposure versus those that were just part of normal nerve cell development.

Understanding Different Groups of Genes

We found that the genes affected by lead could be grouped based on their functions. Some groups of genes were tied to how cells grow, duplicate their DNA, and respond to stress. We discovered that lead exposure was primarily affecting genes involved in cell growth and maintenance.

Notably, we identified some gene clusters that were especially responsive to lead. One cluster included genes related to DNA repair, which are crucial for keeping cells healthy. Another cluster was involved in making proteins, which are essential for various cell functions.

Evaluating the Impact of Lead

By analyzing how many genes were affected at different lead levels, we noticed that even low levels of lead could cause issues. As exposure duration increased, the range of affected genes also expanded. In fact, more than 4,500 genes showed changes at environmentally relevant lead levels by the end of our study.

Looking at Biological Pathways

We took a closer look at how lead impacts specific biological pathways. Some pathways are involved in DNA replication and damage repair, while others are tied to how cells use and produce proteins. Our findings showed that as lead exposure continued, many genes related to these processes were either turned off or expressed less.

The Bigger Picture: How Lead Exposure Affects Health

Our research highlights that exposure to lead during key developmental stages can have significant impacts on brain development. This isn't just a warning for kids today; it connects to the past, as many people were exposed to higher lead levels when it was more common in paint and gasoline.

The implications of our work extend beyond just understanding lead’s impacts. It raises important questions about how these Exposures in childhood may connect to health issues later in life, including neurodegenerative diseases. If lead disrupts the right processes during brain development, we could see those effects manifest in various health issues over time.

Conclusion: The Need for Continued Awareness

In summary, we’ve learned that lead exposure during the development of brain cells can lead to serious changes in gene expression. With harmful effects on essential functions like DNA repair and protein production, these changes raise alarm bells for public health.

While strides have been made to reduce lead exposure, it is clear that we need to continue being vigilant. Monitoring environments where children play and live is crucial to ensuring they grow up healthy and have the best chance at a bright future.

So, as we move forward, let’s keep our guard up against lead and work towards a healthier, lead-free tomorrow. The stakes are too high to ignore this issue any longer.

Original Source

Title: Environmentally Relevant Lead Exposure Impacts Gene Expression in SH-SY5Y Cells Throughout Neuronal Differentiation

Abstract: Lead (Pb) causes learning and memory impairments, but the molecular effects of continuous, environmentally relevant levels of exposure on key neurodevelopmental processes are not fully characterized. Here we examine the effects of a range of environmentally relevant Pb concentrations (0.16M, 1.26M, and 10M Pb) relative to control on neural differentiation in the SH-SY5Y cell model. Pb exposure began on differentiation day 5 and was continuous for remaining days, after which we assessed the transcriptome via RNA sequencing at several time points. The bulk of detected changes in gene expression occurred with the 10M Pb condition. Interestingly, changes associated with the lower two exposures were differentiation stage-specific, with aberrant expression of several genes (e.g., COL3A1, HMOX1, and CCL2) observed during differentiation on days 9, 12, and 15 in both the 0.16M and 1.26M Pb conditions, and which disappeared by the time differentiation concluded on day 18. We observed six co-expression clusters of genes during differentiation, and 10uM Pb significantly perturbed two clusters, one involved in cell cycling and DNA repair and the other in protein synthesis. Benchmark concentration analysis identified many genes affected by levels of Pb at or below the current US standard (3.5g/dL) and these genes were enriched for pathways including stress responses, DNA repair, misfolded protein response, mitosis, and neurotransmitter production. This work highlights potential new mechanisms by which environmentally relevant concentrations of Pb impact gene expression throughout neural differentiation and result in long-lasting implications for neural health and cognition.

Authors: Rachel K. Morgan, Anagha Tapaswi, Katelyn M. Polemi, Elizabeth C. Tolrud, Kelly M. Bakulski, Laurie K. Svoboda, Dana C. Dolinoy, Justin A. Colacino

Last Update: 2024-11-03 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.10.29.620844

Source PDF: https://www.biorxiv.org/content/10.1101/2024.10.29.620844.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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