Whatever magic plunged Sleeping Beauty into an enduring sleep may have been pure evil, but anyone who needs to survive a life-threatening condition or someday wants to venture into deep space only wishes it were possible. Could stasis like this be induced just by flipping a hypothetical switch in the brain?
Humans are far from achieving suspended animation as it is imagined in sci-fi movies. However, neuron signals fired in the brains of mice suggest that there might be a way to find that elusive switch. Mice (which don't hibernate) automatically enter a state of torpor — physical or mental inertia — when weather is harsh and food is scarce. Neurobiologist Sinisa Hrvatin and her team at Harvard Medical School investigated the processes that go on in the brains of these mice when they enter a state of torpor, and were also able to induce and disrupt torpor in genetically engineered mice by stimulating specific neurons.
“Our results suggest that neurons in hypothalamus are a key part of the brain circuit that regulates torpor,” Hrvatin told SYFY WIRE. “We used the FosTRAP approach to label the neurons that were active as the animals naturally enter torpor. We then asked whether by simply activating these neurons we would be able to induce a torpor-like state.”
Torpor drastically reduces energy expenditure by slowing down metabolism, heart rate, and breathing to nearly undetectable levels, along with a simultaneous drop in body temperature. Hibernating animals that cannot endure extreme temperatures enter torpor, and so do non-hibernating animals when they are faced with conditions they would not survive otherwise. The hypothalamus is the part of the brain responsible for homeostasis, which balances physiological processes in the body. This is what made it intriguing to Hrvatin and her team — especially since most of the processes behind torpor are still an enigma.
To see what happens in the brain during torpor, the researchers subjected mice to low temperatures and a lack of food so that state could be induced. Their FosTRAP approach was recently published in Nature. It focused on the Fos gene, which produces proteins that regulate cell proliferation and differentiation as well as signal transduction, the process by which signals zapped between cells are converted into biochemical signals. Many of the intracellular pathways these signals travel through regulate how genes are expressed. Some of the mice had their brains genetically altered to express a chemically activated receptor in those neurons that were most active as they went torpid.
Could something like this be used to see if torpor is possible in humans?
“The FosTRAP approach used transgenic mice to study neuronal pathways and would not be directly applicable to humans,” Hravtin said. “One can imagine that one day approaches that build on our understanding of natural torpor and hibernation could be used in humans.”
Tagging Fos proteins gave away which neurons were switched on as the mice transitioned into a state of torpor. This exposed activity in neurons not just in the hypothalamus, but all over the brain, especially those in areas which regulate functions related to outside phenomena that trigger torpor. It was already proven that hunger and temperature drops induced torpor in the mice, so seeing neurons firing in those areas related to hunger, feeding, and body temperature was expected. Genetic tags also allowed the team to activate and deactivate the areas of the brain in order to turn torpor on and off. Mice could be Sleeping Beauty one minute and wide awake the next.
It remains unknown whether artificial induction of stasis in humans will ever be possible. Even this study did not reveal every single brain function that goes into torpor, but Hravtin is hopeful that it is the beginning of something revolutionary.
“Understanding torpor as an example of how the brain regulates metabolic rate and understanding the cell biology of these hypothermic and hypometabolic states may help us identify new treatments for metabolic disease and brain injury,” she said. “A lot more research needs to be done before we would consider inducing a torpor-like state in humans.”