December 12, 2012
New Study Points To Link Between Brain And Hot Flashes
Connie K. Ho for redOrbit.com — Your Universe Online
The team of investigators was interested in learning more about the biological mechanism behind hot flashes, which can affect both males and females and usually includes symptoms like profuse sweating. The scientists found a group of brain cells called KNDy neurons that may serve as a kind of on-off switch for hot flashes.
The neurons are based in the hypothalamus, a part of the brain that manages a number of important body functions as well as acts as the mediator between the central nervous system and hormone signals.
"Although the KNDy neurons are a very small population of cells, our research reveals that they play extremely important roles in how the body controls its energy resources, reproduction and temperature," explained the study´s lead researcher Melinda Mittelman-Smith in a prepared statement. "They are true multitaskers."
The findings of the study were recently published in the Proceedings of the National Academy of Sciences.
"KNDy neurons respond to circulating estrogens," Mittelman-Smith explains. "When these hormones are at very low levels, as is the case in menopause, these neurons go haywire if you will. They grow very large and manufacture several times more neurotransmitter than they did with estrogens present."
The researchers looked at KNDy neurons in rats and developed an animal model of menopause to explain how the biological mechanism of temperature controls would respond to a withdrawal of estrogen, a hormone that initiates the changes that occur along with menopause. The scientists found that the rats whose KNDy neurons were inactive also had a lower skin temperature. Based on these findings, they believe that the neurons control the process by which the blood vessels are widened to increase blood flow through the skin, a biological phenomenon known as vasodilatation.
"The hallmark of hot flashes is vasodilatation," noted Rance, who also works as a neuropathologist at the University of Arizona Medical Center. "When you flash, your skin gets hot and you can see the redness of the skin. It is an attempt of the body to get rid of heat, just like sweating. Except that if you were to measure core temperature at that point, you would find it is not even elevated."
The study used rats because their skin temperature also goes up following the removal of ovaries in a process that mirrors menopause in women.
"Rats regulate heat dissipation with their tail because the rest is covered by fur," added Rance in the statement. "In rats without ovaries, the lack of estrogen causes vasodilatation, which we can measure as increased tail skin temperature."
The scientists then compared the results of the rats of intact KNDy neurons to the rats with inactive KNDy neurons, and found that the skin tail temperatures were lower when there was no KNDy activity.
"They have lower levels of vasodilatation," Rance said. "It is very consistent. Their tail skin temperature is lower than rats with normal KNDy neurons and stays low. It doesn't matter if they have estrogen or not; it doesn't matter if it's night or if it's day."
Rance was unsurprised that some of the same neuronal switches that are important for reproduction also play a role in thermoregulation.
"Being able to regulate body temperature is very important for the species and also for reproduction because it is important for a pregnant woman to avoid extreme hyperthermia. Hot flashes are a symptom of hyperactivity of these neurons."
Even with these results, the researchers believe that KNDy neurons are not the main center for regulating body temperature.
"These animals would be in much more trouble if that were the case," Mittelman-Smith said. "In fact, I don't view KNDy neurons as a thermoregulatory center at all, but rather a group of cells that has the ability to influence thermoregulatory centers."
The researchers believe that this is a step in the right direction in terms of understanding hot flashes.
"Obviously we can't do these studies in women, and only if we understand the mechanism is there a chance of developing therapies. All that is known so far is that dwindling estrogen levels have something to do with it but anything after that is a black box," said Rance.
"Right now the only effective way of treating flashes is estrogen-replacement therapy. If we could figure out what is causing those flashes, we could try to develop a better, more targeted therapy."