Recent research has revealed that the damage caused by smoking may not be limited to its well-known effect of reducing oxygen reaching the brain, but may extend to include a disruption in communication between the lungs and the brain due to nicotine.
It was already known that smoking greatly increases the risk of dementia, with a 2011 study finding that excessive smoking in middle age doubles the risk of developing dementia and Alzheimer's more than twenty years later.
However, dementia is one of the least studied effects, because smokers often die at an early age before symptoms appear.
The new discovery, published by the University of Chicago in the journal Science Advances, reveals a previously undiscovered pathway from the lungs to the brain via rare cells called pulmonary neuroendocrine cells (PNECs). When these cells are exposed to nicotine, they release small molecules known as exosomes, or extracellular vesicles, which disrupt the iron balance within nerve cells, leading to symptoms similar to those seen in dementia patients.
Researcher Cui Zhang from the University of Chicago explains that this research proves the existence of a "clear axis between the lung and the brain" that helps explain the relationship between smoking and mental decline, and opens the way to protecting nerve cells from smoke-induced damage.
The team emphasizes that the lung is not just a passive organ affected by smoke, but rather "an active organ that sends signals that affect the brain," according to Assistant Professor Joyce Chen.
Pulmonary neuroendocrine cells act as important sensors in the airways, but they are very rare (less than 1% of lung cells), making them difficult to study.
To overcome this problem, the researchers generated copies of it in the laboratory using human stem cells.
When these cells are exposed to nicotine, they release enormous quantities of exosomes rich in a protein called serotransferrin, which regulates the flow of iron in the blood. This effectively means that every puff of a cigarette causes the lungs to send the body incorrect signals to change how it handles iron.
The vagus nerve (which runs from the brain to the chest and abdomen) then carries these disturbed signals back to the brain, leading to iron imbalance, oxidative stress, an d dysfunction of the mitochondria (the cell's "powerhouses"), all of which are well-known hallmarks of neurodegenerative diseases.
The team is continuing its research to determine whether preventing the release of these exosomes could have therapeutic uses.
Although applying this to humans is still a long way off, this discovery is an important step in understanding how the lungs and brain communicate, and opens new horizons for preventing smoking-related dementia and neurodegenerative diseases.
