Withstand Psychiatric Stress: Jumping Gene Strongly Linked to Depression, Fear, and Anxiety

Scientists have revealed that a well-known gene functions to survive mental stress by fusing neuroscience and molecular biology.

Tob, a well-known gene, has been discovered to play a substantial impact in lowering melancholy, fear, and anxiety, according to research.

This result was obtained following a number of various mouse-based cell biology and neurological experiments.

Additionally, they found that, but not for anxiety, the Tob gene in the hippocampus was crucial for lowering fear and sadness. That appeared to be under the control of a different area of the brain.

Furthermore, even after several days passed, the experimental mice without the Tob gene remained to exhibit elevated levels of fear manifested as freezing, suggesting that they did not learn that a place wasn't all that unpleasant.

According to the researchers, learning about this function of the Tob gene in anxiety, dread, and depression could have significant ramifications for creating treatments for psychiatric stress.

The Tob gene was initially identified in 1996 by the old Japanese laboratory of Professor Tadashi Yamamoto. It is now widely known for its part in cancer. It may also play a part in controlling the cell cycle and the body's immune response, according to earlier study. Researchers from the Okinawa Institute of Science and Technology (OIST) have learned that this gene also has a significant role in lowering depression, fear, and anxiety in a recent multidisciplinary study that blends molecular biology with neuroscience. Recently, the journal Translational Psychiatry published their research.

Lead author of the study Dr. Mohieldin Youssef stated, "This research is about understanding stress-resilience. He was formerly a PhD candidate in Prof. Yamamoto's Cell Signal Unit at OIST. The gene contributes to stress resilience when it is present, while depression, fear, and anxiety rise when it is not.

Fear and depressive-like behaviors are brought on by tob deletion. The changed functional connection between the hippocampus and the pre-frontal cortex can be used to explain this. The excitation and inhibition of the neurons in the hippocampus increased. Other genes and proteins were also affected. Source: OIST

The Japanese verb "tobu," which means to soar or jump, inspired the name "Tob." This is due to the cell's protein levels becoming more active when it is exposed to a stimulus. Dr. Youssef claimed that because the gene responds so quickly, it has been categorized as an immediate-early gene.

The Tob gene is linked to a variety of events, but studying the brain system is extremely difficult, according to Prof. Yamamoto. Although it had been hypothesized before, this study is the first to prove that Tob protects the brain from stress.

They came to the conclusion that this gene is connected to anxiety, dread, and depression based on the findings of numerous research. The Tob protein levels increased as expected after the researchers stressed out the mice. Then, they utilized mice born lacking the Tob gene and noticed an increase in depressive, frightened, and anxious behavior. For instance, if a mouse carrying the Tob gene were dropped into a pail of water, the mouse would swim and attempt to get out. A mouse lacking the Tob gene, however, simply floated. One way researchers can tell if an animal is depressed is if it lacks the motivation to confront a challenging circumstance.

a pre-frontal brain and hippocampal MRI after the Tob gene was deleted. With the aid of this MRI, the researchers were able to establish that there had been a change in the connectivity between the hippocampus and the pre-frontal cortex. The photograph was taken from the news article "Jumping gene discovered to be closely associated to depression, fear, and anxiety." Source: OIST

The mice lacking the Tob gene also appeared incapable of learning. Dr. Youssef added that when mice are left in an environment that triggers fear memories on a daily basis, they typically come to realize that it isn't all that horrible and cease being scared. Even after several days, those without the Tob gene continued to exhibit elevated levels of fear manifested as frozen.

The researchers then collaborated with Dr. Hiroaki Hamada from the Neural Computational Unit, a former PhD student of OIST. An MRI revealed that when the Tob gene was deleted, the connectivity between the hippocampus and the pre-frontal cortex—two critical regions controlling the brain's resilience to stress—was changed.

Following this discovery, the researchers began to investigate the precise function of the gene in the hippocampus. The Tob gene was directly injected into the hippocampus of mice lacking the Tob gene, but was left absent from the rest of the body. The mice's despair and terror levels returned to normal, but their anxiety levels remained elevated. The researchers then looked at the reverse scenario; they developed a mouse that has the Tob gene in the rest of the body but not in the cells in the hippocampus. They discovered that the mice in this instance exhibited normal levels of anxiety but higher degrees of dread and despair.

Dr. Youssef said, "We've shown that the Tob gene in the hippocampus inhibits fear and depression. But another area of the brain must control the suppression of anxiety.

Next, researchers from OIST's old Brain Mechanisms for Behavior Unit assessed how well the mice without the Tob gene's hippocampus' neurons were functioning. They discovered that while inhibition was reduced, excitement was raised, indicating that the overall balance had changed, which would have an effect on the mice's behavior.

Finally, after subjecting the mice to stress, the researchers performed genetic studies. It's interesting to note that tension didn't immediately alter facial expression. But everything changed when the mice were stressed for 15 minutes. If the Tob gene was deleted, it had an effect on other genes and proteins. This suggests that the Tob gene probably affects a variety of things both directly and indirectly.

Finding out how the Tob gene affects fear, despair, and anxiety could have a significant impact on the creation of treatments for mental stress, according to Dr. Youssef.

By OKINAWA INSTITUTE OF SCIENCE AND TECHNOLOGY (OIST) GRADUATE UNIVERSITY