What exactly makes you thirsty? Dehydration, obviously, but how does your brain know that your body needs water? And how does that grey, squishy lump resting in your cool and comfortable cranium, know when your body needs to heat up or cool off? Scientists at the McGill University Health Centre Research Institute (RI-MUHC) and Duke University have asked themselves just that, and being scientists, went ahead to find out.
They identified a protein in the brain that they think is the key to understanding body hydration and temperature control. Their findings could have huge implications in clinical science, allowing treatments for health issues associated with the imbalance of bodily fluids -- a common sight in the emergency room -- to be developed. Their work was recently published in the print issue of Cell Reports.
“We have identified what we think is the first protein that could allow the brain to monitor physiological temperature and it is important because this protein contributes to how the brain detects heat and triggers adaptive responses such as thirst,” says Dr. Charles Bourque, the study's lead author and a researcher at the Centre for Research in Neuroscience at the RI-MUHC and at the Faculty of Medicine of McGill University. “This protein, which is an ion channel, that regulates the flow of ions across the cell membrane, is thought to play a crucial role in balancing body fluids (water, blood, etc.) and sodium (salts) levels, and changes in its regulation could be involved in linking salt to hypertension, and provoking fluid retention following cardiac failure, sepsis or brain trauma.”
The team led by Dr. Bourque is looking into how the brain performs osmoregulation -- keeping the salt and water balance across membranes all through the body. Even slight osmotic imbalances can have major health consequences, with high salt levels increasing blood pressure and taking a big toll on the kidneys. Low sodium levels, on the other hand, hyponatremia, cause brain cells to swell, causing nausea, vomiting and headaches. It is known to be a very common problem in older adults and it can result in changes in cognition and even seizures.
Imbalances in the body's fluid and salt levels are among the most common reasons for hospitalization after admittance to the ER, says Dr. Bourque.
‘’Now that we have discovered the protein's structure, we can try to understand how this ion channel is involved in conditions such as hyponatremia. This would give us tools to modify the channel’s mechanism of action and either prevent or treat the condition,’’ says study’s first author, Cristian Zaelzer, Postdoctoral Fellow in Dr. Bourque’s laboratory at the RI-MUHC.
This breakthrough rests on previous work Dr. Bourque's team performed at a laboratory in the Montreal General Hospital of the MUHC in 2006. They demonstrated the importance of the TRPV1 gene -- it plays an essential role, in detecting and informing of changes in our bodies fluid balance. Two years later, in 2008, they discovered that the same gene also had a part to play in keeping tabs on the bodily temperature. However, they only managed to do so indirectly -- the protein that TRPV1 holds the blueprints for was still unknown. Until now:
“Collaborating with Dr. Bourque’s group led to identification of a long sought-after TRPV1 ion channel that functions in neurons, making them sense osmotic pressure and temperature ,” explains senior co-author Dr. Wolfgang Liedtke, associate professor of neurology, anesthesiology and neurobiology at Duke University. “This ion channel becomes active during dehydration, switching on the neurons in a part of the brain called the hypothalamus, which instructs the body to act in order to maintain its fluid balance. This can be achieved by triggering a sense of thirst, and also by the secretion of vasopressin – an antidiuretic hormone that acts to promote the retention of water by the kidneys – to maintain body fluid balance.”
“Interestingly, our work also shows that the ion channel is an alternate product of the gene TRPV1 that normally codes for the capsaicin receptor that detects “hot’’ chilli peppers, adds Dr. Bourque. It is like nature has engineered a salt receptor out of a pepper receptor.”