Why lead is (still) bad for your brain

Image credit: Ionut Stefan

Talking about lead is boring. I would know, I’ve spent quite a bit of time trudging through papers about lead while writing this post and the best opening I could come up with is just how mind-numbingly boring lead is. Sadly, boredom isn’t a good indicator for importance. While the days of enthusiastically throwing lead into whatever we could (from water pipes to gasoline to cosmetics to paints for houses and children’s toys) are over, the lead we’ve pumped into the environment doesn’t give up so easily. And if that wasn’t enough, we’ve still found some use cases to keep it hanging around (why yes, I’m talking about batteries).

Ok, but how bad can it really be? The levels of lead are surely not as high anymore, so it’s not really that dangerous, right? Well… short answer: it’s a bit more complicated. The long answer is the rest of the article.

What is lead?

Lead is a heavy metal. (Little side note: until the writing of this article, I’ve taken the term “heavy metal” pretty much for granted, because everyone knows what a heavy metal is, right? Right? Well… apparently there’s quite a bit of ambiguity surrounding the term, but lead is one of the few who meets all of the definitions out there. And heavy typically refers to dense and/or less chemically reactive, i.e. not interested in playing well with others.) So lead is a heavy metal and it’s found naturally in the ground. What makes it pretty neat is that it’s both malleable, but also durable and versatile.

What makes it less neat is that it’s so malleable, versatile, durable, and toxic. As I mentioned in the beginning, lead has been used in a lot of products. And it’s been used since as far back as Roman times. The problem is that lead is so durable, it basically doesn’t degrade. You see, unlike other fun toxic metals, such as mercury (which can be converted in less toxic forms by bacteria), lead is resistant to chemical breakdown, so once you’ve got lead particles in the environment, they will stay there kind of forever, unless you actively remove them somehow. In other words, even if we were to completely stop mining for and using lead (which we aren’t, since the lead-acid battery market is projected to increase in the next years), we would still need to deal in a safe manner with what has been put out there.

Of course, since we’ve stopped putting lead in gasoline (and paints, and cosmetics etc.), things have improved. For example, in the US, levels of lead in blood samples have markedly decreased since 1976. But a decrease doesn’t mean they’ve reached zero. And while many things with negative effects don’t really harm you in small doses, lead isn’t one of them. There is no safe level of lead exposure. What’s more, an average decrease in the US population doesn’t translate into a decrease of the same magnitude across the world, or even across various subgroups of the US population.

Effects of lead and mechanisms behind them

We’ve already established that no amount of lead is safe, but still, the effects of lead exposure on the nervous system don’t occur in an all or nothing manner. They depend strongly both on the level of lead to which one is exposed (more is worse), and the developmental period when exposure occurs (children are more affected than adults).

Lead usually enters the body via one of two routes: either the gut or the lungs. Children absorb more lead than adults because their gut and lung linings are immature compared to adults, allowing more lead to pass through. They also need more iron, calcium, and zinc, metals with which lead is in direct competition (and obviously winning). In addition, small children can be simply more exposed to lead as they have the tendency to put both their unwashed hands, as well as potentially contaminated objects, in their mouths.

While the half-life of lead in the blood (meaning the amount of time needed for the concentration to drop to half) is relatively short, at only 28 days, that’s not the same as the half-life in the body. Some of the lead in the blood will not be eliminated, but it will actually go into the soft tissue, i.e. kidneys, liver, brain, where the half-life is a few months, and more annoyingly, into the bones, where the half-life is between 10 to 30 years. What’s more, from here, lead can leach back into the bloodstream, from where it can once again get into the soft tissue and cause more damage. This happens particularly in pregnancy, thus affecting the unborn babies, but it also occurs during normal ageing, and even more so in conditions such as osteoporosis.

Now, acute effects of lead exposure are pretty clear. If someone were to chomp down on a piece of lead, it would result in seizures, coma, and possibly death. But obviously that’s an unrealistic scenario and not what most people are exposed to. Chronic lead exposure, on the other hand, causes lead to accumulate in the body and it has been linked to memory problems (including development of Alzheimer’s disease later in life), as well as cognitive and behavioural problems, including attention deficits, increased aggression, learning problems, and decreased IQ. But here’s the kicker: in the past, these problems were thought to appear only above certain concentrations: above 10 μg/dL, above 5 μg/dL, above 3.5 μg/dL… And yes, the higher the concentration, the worse the effects. Nevertheless, as research has progressed, it’s become clearer and clearer that there is no safe exposure to lead. Even very small concentrations can cause neurological effects.

But what are the molecular mechanisms behind that? (Side note: directly relating one specific molecular disruption to one specific behavioural outcome doesn’t really work, but we can correlate the effects we observe at the behavioural level with the in vitro molecular data to get a clearer picture of how lead wreaks havoc on the nervous system.) So far, three main ones have been identified. Lead alters the fluidity of the cellular membrane, it interferes with calcium-based processes, and it generates reactive oxygen species.

Regarding the cellular membrane, it’s important to understand that it is neither static, nor uniform. On the one hand, there are many proteins embedded in the membrane that basically move around to where they’re needed. On the other hand, the cell membrane has a lot of traffic in the sense of vesicles that either fuse with it, or bud off from it. In particular for neurons, think of synaptic transmission: vesicles from inside the membrane fuse with it to release neurotransmitters, then new ones form where more neurotransmitters are packed, and all this happens under strict control from membrane proteins. To ensure optimal functioning of this process, the fluidity of the membrane needs to be just right: either too much or too little will mess things up.

Calcium is an ion which plays a very important role in regulating synaptic transmission and thus facilitating communication between neurons. Sadly for it, calcium resembles lead quite a lot, so proteins can easily mistake them, and lead forms stronger bonds with these proteins. But while lead can easily steal calcium’s spot, due to small differences in chemical behaviour and in shape, it’s not able to perform the same functions. Instead, it kind of remains stuck in there and jams the system.

Finally, reactive oxygen species, or free radicals, as you might know them, appear partly because of lead’s interference with calcium signaling, but also because lead inhibits antioxidant enzymes, and disrupts mitochondrial function. Reactive oxygen species, in turn, can damage DNA, lipids, and proteins, further exacerbating negative effects in the nervous system.

What is there to do?

Panic for the sake of panic is useless (one could even say it’s harmful). So what can we do? First, we said the effects are worse in children, so if they were exposed to lead, is that it? Are they pretty much doomed to suffer the consequences? Not necessarily. Some studies show that enriched environments and early behavioural interventions can reverse some, if not all effects associated with early life lead exposure.

Still, prevention is better than intervention, but you might be wondering, how big of a thing is lead exposure still? After all, we figured out a long time ago that lead isn’t good for us (even the Romans knew that) and we’ve already done a lot to get rid of it, no? Well, yes and no. There have been real improvements, especially in removing lead from gasoline, paint, and plumbing. But, as with a lot of other issues, it tends to come down to where you live. As you can imagine, there are relatively pronounced differences between countries, but even within the same one, your ZIP code still matters. Older housing, industrial sites, ageing infrastructure, and underfunded communities all play a role in how much lead still lingers in your air, water, soil, and body.

A few steps to keep in mind for protecting yourself against lead exposure are the following. If you think you might have lead in your home paint or pipes, try to get rid of them in a safe way. If you know there’s lead somewhere in your community, try to get involved and push for programs that promote its removal. And even if the issue doesn’t directly impact you, you can still volunteer to help those who might suffer from it.

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