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Use of miR-17-92 gene cluster in preparation of medicines for treating mental diseases

A gene cluster, spiritual technology, applied in gene therapy, nervous system diseases, drug combination, etc., can solve problems such as ignorance

Active Publication Date: 2015-08-12
涛慷神经医疗研究院(厦门)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Altered expression of miRNAs has been found in the brains of some patients with anxiety, but we still don't know exactly which miRNAs play a role in anxiety and depression, and in response to antidepressant drugs

Method used

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  • Use of miR-17-92 gene cluster in preparation of medicines for treating mental diseases
  • Use of miR-17-92 gene cluster in preparation of medicines for treating mental diseases
  • Use of miR-17-92 gene cluster in preparation of medicines for treating mental diseases

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Experimental program
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Effect test

Embodiment 1

[0023] Published research indicates that chronic stress can induce anxiety in mice. Applicants first verified whether stress-induced anxiety is related to the expression level of miR-17-92 in the brain. Anxiety was induced in ten-week-old C57 / BL6 mice after being placed in a confined space for two weeks. The applicant extracted RNA from the hippocampal region of the brain and found that the expression of miR-17-92 was significantly reduced ( figure 1 ). This suggests that stress-induced anxiety can reduce the expression of miR-17-92. Further, selective serotonin re-uptake inhibitors (selective serotonin re-uptake inhibitors, SSRI) fluoxetine (fluoxetine) is currently commonly used antidepressants. Applicants administered fluoxetine while stressing ten-week-old mice. The applicant found that the use of antidepressants can significantly increase the expression of miR-17-92 in the hippocampus of the mouse brain ( figure 1 ). This suggests that miR-17-92 acts on antidepressa...

Embodiment 2

[0025] In order to study the specific function of miR-17-92, the applicant bred miR-17-92 conditional knockout mice (knockout, KO). In Nestin-CreER tm After mating mice with floxed miR-17-92 transgenic mice, Cre activity can be induced only under the condition of injecting tamoxifen (Tamoxifen) to knock out the expression of miR-17-92 in the hippocampal region of the adult brain. This conditional knockout mouse, called miR-17-92KO. At the fifth week of age, mice were injected with Tamoxifen for 5 consecutive days to activate Cre activity and knock down the expression of miR-17-92. When the mice were at the ninth week of age, the applicant tested the learning and memory ability of the mice using the classic Morris water maze test. Mice were placed in a circular water maze with a diameter of 1 m. There is a platform hidden in the water maze, and the learning and memory ability of mice can be inferred by testing the time for mice to find the platform. The applicant found that...

Embodiment 3

[0027] Surprisingly, applicants found that knocking out the miR-17-92 gene resulted in behaviors similar to anxiety and depression in mice ( image 3 ). In the open field experiment (open field), mice were placed in an open space of 50 cm X 50 cm. Because mice are more afraid of exposure to open space and light, the more anxious the mouse, the more it will avoid open space and light. Therefore, we can judge the anxiety level of the mice by testing the time the mice stay in the open space and the distance they crawl. The applicant's results show that miR-17-92 knockout mice rarely stay in the center of the open field, indicating that reducing the expression of miR-17-92 in the brain leads to increased anxiety symptoms in mice ( image 3 ). This suggests that miR-17-92 can serve as a new pathological marker for anxiety and depression.

[0028]In summary, since depression and anxiety disorders have many comorbidities, antidepressant therapy is commonly used in clinical treatm...

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Abstract

The invention relates to a use of miR-17-92 gene cluster in the preparation of medicines for treating mental diseases. The use is of real significance to basic researches and further clinic application, and new protein encoding genes and untranslated miRNAs having a response effect to antidepressants are detected through the miR-17-92 gene; related research visual field is developed to lay a good foundation for development of new antidepressants; and new anti-depression targets can be developed, miRNA is a micro-molecule, can be extremely easily synthesized in vitro and can be introduced into cells, so the control of the expression level of the miRNA in vivo becomes possible.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to the use of a miR-17-92 gene cluster in the preparation of medicines for treating mental diseases. Background technique [0002] Mood disorders are on the rise due to genetics, environment and the fast pace and stress of modern life. In China, the incidence rate of depression is 3%-5%, and it is estimated that there are 30 million people with depression. Only surveys in several provinces such as Hebei and Zhejiang show that the prevalence of anxiety disorders is between 5% and 7%. However, due to the low rate of patient visits in China, the number of patients with anxiety and depression may be higher than the statistics. Anxiety disorders affect 40 million adults in the United States each year. After experiencing the fear and helplessness brought about by long-term anxiety, patients are likely to have severe emotional loss, such as suicidal tendencies. Countries around the w...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P25/24A61P25/22A61P25/18
Inventor 孙涛
Owner 涛慷神经医疗研究院(厦门)有限公司
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