Stimulation of the hypothalamus have introduced mice to torpor

In the hypothalamus of mammals that do not hibernate, have found neurons, the activation of which slows down your metabolism for up to two days, reported in two articles by independent groups of scientists (1, 2) in Nature. Likely structures for hibernation in animals, and in some form has survived even those who she enjoys. Possible practical benefit of these studies is that “neurons hibernation” can be activated at the right time and thus slow down the tissue damage or to preserve donor organs.

Endothermy animals a large amount of energy is spent to maintain body temperature constant. Than the body smaller, the harder to do as more relative heat loss. In the cold season and (or) if there is insufficient food to maintain the desired body temperature becomes more difficult. One of the ways to survive through unfavorable periods is to slow down your metabolism: eat smaller and allot less heat. It does not turn out to move as hard as usual, so that the animal seeks refuge and spends a period of rest lying down in it.

Hibernate (hibernation; the so-called long period of dormancy in warm-blooded animals) is an active process, the animal while it is able to regulate body temperature, as in normal conditions. But what triggers hibernation and allows you to change the temperature at the time it is not too clear. It is clear that this is part of the Central nervous system. Since the main thermoreceptors located in the hypothalamus, the core structures governing dormant, began to search there.

It is known that neurons in different areas of the hypothalamus secrete QRFP (the peptide). Their activation or introduction of QRFP into the lateral ventricles of the brain reduces body temperature and locomotor activity of mice, which is characteristic of hibernation. However, it was not clear which peptide-producing neurons provide hibernation and on which cells do they operate in the first place.

To find out, neuroscientists from several Japanese institutes led by Takeshi Sakurai (Sakurai Takeshi) was injected transgenic mice AAV viral vectors with the red fluorescent protein mCherry, an improved activated Cre-recombinase (iCre), in different parts of the hypothalamus, where the generating and iCre QRFP neurons. In these neurons were also “designer receptors”that interact only with artificial created substances-ligands. Introducing into the peritoneal cavity of mice the corresponding ligands, the researchers activated QRFP and iCre-producing neurons, and the latest in brain slices could be seen because of mCherry. Spent optogenetics and a series of experiments where the same neurons are stimulated by light.

The activation of the neurons was monitored by electrophysiological methods, and body temperature of the mice was determined by sensors sewn into the abdominal cavity of rodents. So the researchers determined exactly which neurons are responsible for slowing metabolism in the mice (it was expressed in the drop in body temperature and reduced motor activity). Generally speaking, the laboratory mouse not hibernicum, but may fall into the short-term state of inactivity — Tabor. The experiments were repeated on rats, which is neither hibernation nor torpor.

However, in both species of rodents stimulation of QRFP neurons of the medial preoptičeskoj area and anteroventral periventricular nuclei of the hypothalamus led to the fact that animals have decreased body temperature for up to 48 hours, and with it the rate of metabolism and motor activity. This condition in their properties was like torpor. The autopsy of the animals revealed that several hours of a slow metabolism do not harm the internal organs. The behavior of rats and mice after the numbness also did not change significantly.

When the neurons that produce QRFP and thus slow down the metabolism (they are called short Q-neurons), were forced to develop a green fluorescent protein, it became clear what kind of cells they are pulling the axons, the neurons of the hypothalamus dorsomedial. Optogenetics periodic activation of these axons has led to the fact that the body temperature of the animals decreased by a few hours. Experiments with selective blocking Q-neurons showed that among them are excitatory (secrete glutamate) and inhibitory (secrete gamma-aminobutyric acid) cells, and even those that operate in two ways (secrete both neurotransmitter). To similar conclusions came the group Michael Greenberg (Michael Greenberg) from Harvard medical school.

What is the role of the Q-neurons in normal physiological conditions, animals are not capable of hibernation (mouse) or even torpor (rats), is not yet clear. Probably they provide a quick reduction in body temperature. But if their help was able to reach the hours-long state of torpor in rodents, it is not inclined, it is possible to assume that selective manipulation of these neurons will help to slow down the metabolism of other species, including humans. And low metabolic rate tissues and organs persist longer in their original state. Thus, the induced catalepsy can be used to increase the “shelf life” of donor organs.

We wrote about hibernation and other periods of rest in animals in the material “Thugs”. Mammals, especially small ones, often wait out adverse conditions, reducing the intensity of metabolism. Birds almost never do: it is easier to change the location and go somewhere where is warmer and more feed. The only exception is an American rock Nightjar. Although he is able to fly, in some parts of the range Nighthawk to weeks included in a state close to hibernation. To the list Guberniya birds can join the rocky new Zealand Wren: in April 2020 published an article, which the authors suggestthat he, too, falls asleep.

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