其他摘要 | Anxiety disorder as a very common mental disease in today's society, its etiology is not clear, its pathogenic factors may include genetics, personality characteristics, cognitive patterns, external events stimulation, etc.. Clinical treatment of anxiety disorders is mainly cognitive behavioral therapy and drug therapy. However, even after treatment with multiple anti-anxiety drugs, nearly 40 percent of patients had no or minimal response. Therefore, we need to conduct in-depth research on the basic physiological mechanism of anxiety disorders, so as to find therapeutic targets for its basic mechanism.
With the further study of mitochondrial oxidative phosphorylation, more and more evidences indicate that mitochondrial dysfunction is involved in the pathological process of anxiety disorders. In the new study, the researchers propose a treatment mechanism involving mitochondria. Studies have shown that mitochondrial function is altered in high-anxiety animals, and that the use of compounds targeting mitochondria can improve anxiety-like symptoms. Therefore, it is necessary to study the biological essence and mechanism of anxiety disorder from the perspective of abnormal mitochondrial energy metabolism, and explore the regulatory mechanism of mitochondrial function. A large number of studies have revealed that the Adenosine 5 '-Monophosphate-Activated protein kinase/Sirtuin1 (AMPK/SIRT1) pathway affects mitochondrial function by regulating mitochondrial biosynthesis. Therefore, this study intends to establish an anxiety model in rats by using uncertain empty bottle drinking stress, and observe the changes in mitochondrial energy metabolism mediated by AMPK/SIRT1 pathway in amygdala and medial prefrontal cortex, so as to reveal the anti-anxiety mechanism of this pathway.
In this study, the following three studies were carried out: Study 1 used the uncertain empty bottle drinking water stress model to establish the animal anxiety model, and the elevated Cross maze (EPM) and open field (OFT) tests were used to investigate the anxiety level of the control group and the model group on the 7th, 14th and 21st days of stress. Study 2 Transmission electron microscopy was used to observe the morphological changes of mitochondria in amygdala and medial prefrontal cortex. In study 3, the changes in mitochondrial energy metabolism mediated by AMPK/SIRT1 pathway in amygdala and medial prefrontal cortex were observed, and the expression levels of AMPK/SIRT1 pathway-related proteins were determined to clarify the possible relationship between AMPK/SIRT1 pathway-mediated mitochondrial energy metabolism abnormalities and the pathogenesis of anxiety disorders.
The results showed that the mitochondrial structure of model group rats was damaged, the mitochondrial energy level was decreased, and the expression level of AMPK/SIRT1 pathway related protein molecules was significantly decreased. These results suggest that mitochondrial energy metabolism is related to anxiety-like behavior, and AMPK/SIRT1 pathway is involved in the corresponding anxiety pathological process. Studies have shown that AMPK/SIRT1 pathway mediated mitochondrial energy metabolism disorder is the main mechanism of anxiety disorders, providing a new theoretical basis for anxiety related research. |
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