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Two separate studies identify & activate neurons in mice to induce hibernation, hinting at suspended animation in humans.

two separate studies from Harvard and RIKEN researchers identify neurons capable of inducing hibernation-like states in mice when they are stimulated. The team states their findings point to the possibility of inducing torpor in humans which could have ramifications for brain injury prevention during a stroke, increasing survival rates for heart failure in the ER due to serious trauma or enabling new treatments for metabolic diseases, as well as developing stasis techniques for trips to Mars.

The core body temperature of a mammal is highly controlled being maintained at roughly 37° C throughout life. However, a short supply of food can cause some mammals to enter a dormant state known as torpor or hibernation where the animal’s body temperature and metabolism decrease to conserve energy.

The ability to preserve energy and decrease metabolism on demand holds great potential for a wealth of applications regarding human health, with a hibernation-like state possibly helping a person survive serious trauma. It is also predicted this induced torpor will lead to long-term suspended animation to enable deep space travel.

Long-term torpor in the ER

Now, two separate studies from Harvard and RIKEN researchers identify neurons capable of inducing hibernation-like states in mice when they are stimulated. The team states their findings point to the possibility of inducing torpor in humans which could have ramifications for brain injury prevention during a stroke. This, in turn, may increase survival rates for heart failure in the ER due to serious trauma or enable new treatments for metabolic diseases, as well as developing stasis techniques for trips to Mars. Both studies have been published in the journal Nature here and here.

Previous studies show when an animal goes into a short-term torpor or long-term hibernation, the physiological processes in their body drastically decrease. Recent studies have replaced blood with ice-cold saline to markedly slow biological systems, preventing cell death in severe trauma. Saline transfusions, however, risk damaging tissue, with engendering an animal into dormant-state presenting a better solution.

The hypothalamus has been shown to play a key role in the thermoregulation animals utilize to achieve hibernation. Therefore it is highly desirable to gain a greater understanding of the specific neurons in this brain region playing a central role in this process. The current studies have mapped neural circuits possessing the ability to send mice into a dormant state when manually activated.

Inducing torpor in animals

The first study investigates a group of neurons called quiescence-inducing neurons, or Q neurons located in the hypothalamus, a brain region important for thermoregulation.

Because Q neurons express a neurotransmitter called QRFP, the team decided to test the role this peptide plays in thermoregulation. They did this by engineering mice to express QRFP when they were injected with a small molecule called clozapine N-oxide.

Results show when Q neurons are stimulated, they trigger a hibernation-like state in mice, reducing their body temperature and metabolism for over 48 hours, a period significantly longer than natural torpor cycles in these animals. Data findings show the type of thermoregulation mediated by Q neurons is hypothermic-based and primarily regulated by glutamatergic transmission.

Mapping hibernation in the brain

The second study genetically tags neurons activated in the hypothalamus when fasting mice enter torpor, and again after the mice have been fed and their body temperature returned to normal.

Results show fasting-based torpor in mice is regulated by neurons in the medial and lateral preoptic area of the hypothalamus to produce a greatly decreased metabolic rate and a body temperature as low as 20 °C.

Data findings link the largest subset of these neurons to the neurotransmitter PACAP, whose stimulation was demonstrated to trigger torpor, whilst dampening these neurons was shown to disrupt the normal torpor cycle of the mice. The groups note an apparent overlap between the neural circuitry identified in both studies involving PACAP and QRFP expression.

Controlling hibernation

The teams surmise they have identified multiple subpopulations of torpor-inducing neurons in the median preoptic nucleus of the hypothalamus. For the future, the researchers state their study proffers improved knowledge and more control of hibernation in mice and other animal models.

Source: Scientific American

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