Schizophrenic rats
Novosibirsk geneticists have developed a unique line of rats for the study of schizophrenia
Nadezhda Dmitrieva, "Science in Siberia"
What do Vaclav Nijinsky and a laboratory rat that freezes at the touch have in common? Unfortunately, nothing good. Experimental animals of a unique genetic line, bred by Novosibirsk scientists of the Institute of Cytology and Genetics SB RAS, are used as model animals for the study of schizophrenia. This disease was also diagnosed in the world-famous dancer and choreographer.
Doctors are still arguing about the causes of schizophrenia, and ICiG SB RAS specialists are trying to find patterns of the disease development by modeling it on rats. The founder of the study, Doctor of Biological Sciences Viktor Georgievich Kolpakov, created an original line of rats of "genetic catatonia", prone to spontaneous freezing and involuntary arousal.
It should be noted that catatonic reactions have two poles: immobility and involuntary excitability. Both are present in the rats of the derived line: on the one hand, they are prone to freezing, on the other – "nervous".
– Viktor Georgievich Kolpakov, a psychiatrist by training, observed people with schizophrenia and saw that they freeze in uncomfortable poses. Therefore, he began breeding with "hanging" rats (those that could freeze, clinging to the bars of the ceiling of the cage). He selected three pairs of such animals and began to breed them. Then the animals stopped hanging, Kolpakov tried to lift them with a stick and saw: they also freeze, but in a vertical stance. In the 20s, 30s generations, we recorded rats freezing on the sacrum. You could take them with your bare hands and give them such a pose. In recent generations, the rodent also freezes, but vocalizes, squeaks – that is, a nervous reaction manifests itself," says Tatiana Alekseevna Alyokhina, a senior researcher at the Laboratory of Evolutionary Genetics of ICIG SB RAS, Candidate of Biological Sciences.
The genetic lineage of rats with catalepsy may allow us to find out what biochemical and hormonal changes are characteristic of schizophrenia. The breeding of this line took more than forty years, and, curiously, in the 20th generation, almost all animals were "frozen", and they froze for a few minutes, which is not typical for these fast and nimble animals. Starting from the 40th generation, individual "nervous" individuals appeared among them in the same genetic line, by the 70th generation there were much more "nervous" rats.
– The phenomenon of catatonia is characteristic not only for schizophrenia, but also for additive psychoses such as neuroses, bipolar disorders, depression, and also occurs after post-traumatic stress states. We selected rats that were frozen for a long period, and as a result we got animals with a reduced content of mediators, hormones (including sex hormones), with an increased level of anxiety and fear, with bald spots on the coat and with a lower weight. So today we have a model of schizophrenia, depression and neurosis in the GC line," adds Tatiana Alyokhina.
What is good about the "animal" model: it allows you to find the relationship between the external manifestations of the disease – hardening or increased excitability – and changes in biochemical and endocrinological parameters.
– To study the phase of catalepsy on a person, you need to put him in this state, or wait until he enters there, which, in general, is not available to doctors. In rats of our cataleptic breeding line, the solidification phase can be triggered at will and all kinds of biochemical, hormonal parameters that accompany it can be examined," Dmitry Klochkov, Doctor of Biological Sciences, who has studied rats of the "genetic catatonia" line up to today, describes the advantages of the model.
It is impossible to transfer the results of the study obtained on animals directly to humans, but there is a chance that they will allow us to better understand the course of the disease, to assume what will happen to the patient
– In particular, we study what happens in the brain during freezing episodes, we can divide it into structures and look at the state of mediators – norepinephrine, dopamine and serotonin. Observing several generations of breeding, we found out that mediators are reduced in all brain structures, and most importantly, in the frontal cortex, where all brain monoamines responsible for disrupting complex behaviors, such as learning, are also reduced, – says Tatiana Alyokhina.
Mediators (neurotransmitters) are biologically active chemicals for transmitting electrochemical impulses between nerve cells and from neurons to other cells. The frontal region of the cerebral cortex reaches its greatest development in humans. When the frontal areas are affected, complex motor functions that ensure work and speech, as well as adaptive, behavioral reactions of the body are disrupted in humans.
Another observation of researchers that may be useful for improving the quality of life of patients is the compensatory reaction of rats to a decrease in sexual function. In humans, schizophrenia is often accompanied by a deterioration in reproductive performance, and to study the relationship of the disease with this area, the rat is convenient because it has an accelerated cycle – after four days, certain phases of sexual function can be observed.
– We found an increase in the level of progesterone (the hormone of conception) in females, despite a general decrease in sexual function, – explains Dmitry Klochkov.
It is difficult to say when doctors will fully understand the mechanisms of schizophrenia development, but the fact that the results of scientists from the Institute of Cytology and Genetics of the SB RAS are used in training courses at the I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry in St. Petersburg and in the Novosibirsk Psychiatric Clinic speaks of the unconditional benefits of the model.
– The way to get results and put them into practice is very thorny and difficult. In this case, when it comes to a complex disease, it is not easy to assume what can be useful from these studies in medicine. However, the results already published in 100 scientific articles and 4 monographs are an achievement," adds Dmitry Klochkov.
– In any case, the bred line of rats is unique, it is the only one in the world, and these animals are similar to people with schizophrenia in their appearance, in terms of hormones, and in terms of stress mediators in the brain, – emphasizes Tatiana Alyokhina.
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27.06.2017