Two studies published in the journal Nature have independently zoned in on the brain circuitry that triggers a hibernation-like state in rodents, which they say could have implications for humans.
Core body temperature is very tightly regulated, within about 0.5 degrees around 37 degrees Celsius, but some animals have the remarkable ability to drop their temperature and metabolism to survive harsh environments or food scarcity.
Although studies have pointed to the central nervous system’s involvement, the precise mechanism for this state has been elusive.
“We were fascinated by the phenomenon that many mammals, including some primates, can profoundly reduce their metabolic rate and body temperature and enter states of ‘suspended animation’ such as torpor and hibernation,” says Sinisa Hrvatin from Harvard Medical School, US.
“How animals enter, regulate and survive these extreme states is a fundamental question of homeotherm biology, the understanding of which could have profound medical applications.”
The energy-conserving state is called torpor or hibernation, depending on how long it lasts, during which time animals can lower their body temperature by five to 10 degrees or even more.
Some animals, like mice, might drop their body temperature to 30 degrees daily for brief periods, while others, such as bears, go into long, seasonal hibernation.
Hrvatin and a team from Michael Greenberg’s lab explored this in laboratory mice (Mus musculus), who can instigate torpor by drastically decreasing their metabolism and body temperature by up to 20 degrees when fasting.
Using recent technologies, they showed that stimulating a group of neurons in the hypothalamus, identified as being active during natural torpor, could drive mice into that state, even when there was no food shortage.
The researchers then found they could prevent torpor by blocking those neurons’ activity, confirming their central role in inducing a hibernation-like state.
How animals enter, regulate and survive these extreme states is a fundamental question of homeotherm biology.
Across the Pacific Ocean, a Japanese study, first-authored by Tohru Takahasi from the University of Tsukuba, also associated a distinct group of hypothalamic neurons, called Q neurons, with torpor in laboratory mice.
They genetically engineered the little critters so those neurons could be activated via chemicals or laser light, causing the mice to become immobile and drop their body temperature by more than 20 degrees. They also had slowed heart rate, breathing and metabolism as observed in torpor or hibernation.
The altered state had no adverse effects on mouse behaviour, nor damage to tissues or organs.
This group took it a step further, repeating their experiments in rats – which don’t normally go into torpor or hibernation – and showing that activating the Q neurons still induced a hypometabolic state.
With very different methods, the two studies reinforce each other, write Clifford Saper, from Harvard Medical School and Natalia Machado, from the Beth Israel Deaconess Medical Centre in Boston, in a related commentary.
In so doing, the research challenges previous theories. “This model calls for reconsideration of much of what we thought we knew about thermoregulation,” they write.
Sakurai and colleagues suggest a broad range of mammals might have these brain circuits, including non-hibernating species such as humans.
If humans have similar neurons, Saper and Machado speculate this could help control fever or induce hypothermia and slow down metabolism after events like a heart attack or stroke to reduce tissue damage.