Kyoto University discovered the "reset switch" of the biological clock, to improve jet lag and lifestyle diseases


The biorhythm of many living beings including humans is controlled by the "body clock" that has been formed in the process of long evolution of hundreds of millions of years. Although details of the mechanism have not been known for a long time, the research team of Kyoto University challenges the mystery, it is a type of hormone expressed from the suprachiasmatic nucleus in the headArginine vasopressinAnd the function of its receptor. Based on the research results, we know that we can control the body clock, and it can be expected to be applied to lifestyle diseases due to jet lag and changes in working environment. The research result was published in the science magazine "Science" on 4 October, Japan time.

Succeeded in development of a mouse that does not get jet lag - expected for the development of drugs for the shift worker's delay time syndrome - - Kyoto University

The biological clock of many organisms has a period of about 24 hours and 10 minutes, and based on itCircadian rhythmActivity patterns and physiological phenomena such as "get up, sleep, eat (appetite)" are controlled. Although this biological clock has played an important role for the survival of life, it does not correspond naturally to the change unique to modern society such as the global movement by jet aircraft and the diversification of the life pattern, and "jet lag" It is also a fact that there are problems unique to modern day.

In this study, the optic nerves connecting the left and right eyes and the brain intersectVisual crossoverArginine vasopressin (AVP), a hormone secreted from the nerve cell mass called the "suprachiasmatic nucleus" which exists in the vicinity of the central nervous system, has played a major role in this internal rhythmic mechanism.

◆ "Normal mouse" and "Time lost mouse"
The research team focused on AVP expressed from the neurons of the suprachiasmatic nucleus and their receptors V1a and V1b and clarified their functions. For experiments, two types of normal mice and "time lost mice" with V1a and V1b receptors deleted were used, and an experiment was conducted in which the cycle of brightness of the breeding environment was shifted artificially by 8 hours As a result, it was discovered that the time lost mice react quickly to changes in light and dark environment.

This is the result of the experiment. Normal mice took about 10 days to adapt to the time difference, whereas the time lost mice instantly acclimatizedtime differenceIt has been shown that it has completely disappeared.

In addition, recovery of the expression rhythm of the "clock gene" from which the circadian rhythm is formed on the suprachiasmatic nucleus took only 8 days in normal mice, but only 3 days later in the time lost mice, which is very quick It was a reaction.

At the same time, it has also been clarified that the expression rhythm of the clock gene of peripheral organs such as the liver and kidney and the rhythm of body temperature also recovered earlier than normal mice with time-lost mice.

◆ Control the AVP receptor function and manipulate internal rhythm and jet lag
Based on the above results, the researchers thought that local neural circuits between AVP cells of the suprachiasmatic nucleus via AV1 V1a and V1b receptors contributed to the maintenance of a stable circadian clock system . In other words, thanks to this neural circuit, normal mice can continue to carve their own body clock precisely without being influenced by changes in the light and dark environment of the outside world. The reason why the time lag elimination mice showed rapid adaptation is because this local neural circuit is missing, paradoxically speaking, is not it possible to intentionally operate the body clock by using this mechanism, It came to the idea.

So the research team succeeded in remarkably reducing the time difference by directly administering antagonists of V1a and V1b receptors to the suprachiasmatic nucleus of normal mice.

On the contrary, by manipulating this mechanism intentionally, it is possible to alter the rhythm of the body clock to reduce jet lag, since AVP and V1a and V1b receptors have a major role in establishing the rhythm of the body clock , It is the conclusion of the research team. In addition, although this time is a mouse experiment, similar human suprachiasmatic nucleus exists in the human body, and the AVP neuron system therein exists as the main neuron system, so there is also a similar mechanism in humans It is supposed that it is supposed to be. The research team hopes that this result will lead to the development of new therapeutic drugs for shift workers' pathology such as sleep disorders and lifestyle diseases as well as the time difference associated with traveling abroad.

Dr. Michael Hastings from the UK Medical Research Bureau told British BBC "It is a wonderful research and it is very exciting in this area and it is a big step forward from the past jet lag countermeasures." Meanwhile, "Vasopressin acceptance Because the body has close relevance to the function of the kidneys, it is necessary to pay close attention so that newly developed drugs will not adversely affect the kidneys ".

Although this field is still deepened in research, for example, it is assumed that a time difference occurs in the response of the body clock and the body clock of the brain does not coincide with the body clock of the internal organs, so further detailed experiments and verification are required It is the first time.


in Science, Posted by darkhorse_log