In 1996, Prof. Tadashi Yamamoto’s former lab in Japan first characterized the Tob gene. The Tob gene has a very important role in cancer. According to previous research, the Tob gene plays a very crucial role in regulating the cell cycle and immune system of our body. Recently, Scientists from the Okinawa Institute of Science and Technology (OIST) have discovered that this Tob gene plays a role in reducing depression, anxiety, and depression in a multidisciplinary study that combines molecular biology with neuroscience. Journal of Translational Psychiatry recently published their work.
The name of the Tob gene comes from the Japanese word 'tobu' which means jump or fly. This happens because of the stimulus to which the cell expose, causing the level of protein to jump in activity. "Since it has a very quick response, hence the gene is classified as an immediate-early gene," said Dr.Youssef.
"Tob gene is associated with different phenomena, though it is a very challenging task to work on the brain system," said Prof. Yamamoto. "Despite the fact it was previously suspected, this is the first research that illustrates the Tob gene relation with brain against stress."
Multiple experiments led them to the conclusion that this gene is linked to anxiety, depression, and fear. To find out about the relation between the Tob gene and depression, fear, and anxiety researchers exposed mice to stress, and as they are expected saw increased levels of Tob protein. And they found out this was the opposite in the case of mice lacking the Tob gene, they discovered an increase in phobic, anxious, and depressed behavior.
For example, when both the mice have been placed in a bucket full of water the one with the Tob gene swam and tried to escape from there, but the one without the Tob gene simply floated in the water. By watching this scenario researchers concluded that an animal is in depression, because of the lack of will to fight in a difficult situation. This is one way they assume an animal is depressed. Dr. Youssef explained that when mice with the Tob gene were placed environment that provokes fear memory after sometimes they realized that it is not so terrible and stopped being afraid. But those without the Tob gene continue to express increased levels of fear manifested as frozen.
Then scientists worked together with Dr. Hiroaki Hamada, a former Ph.D. student of OIST, from the Neural Computational Unit. MRI revealed that there was a change in the connection between the hippocampus and the pre-frontal cortex when the Tob gene was removed. To find out more about the function of the Tob gene within the hippocampus they inserted the Tob gene in the hippocampus of the mice (without the Tob gene)while keeping it dormant in another body region. And they found that depression and fear levels in the mice returned to normal but anxiety remained high. Then they performed the opposite, breeding mice with the Tob gene in the rest of the body but lacking in the hippocampus. They found anxiety levels were normal but elevated levels of fear and depression.
We have concluded that suppression of fear and depression is done by the Tob gene present in the hippocampus but the suppression of anxiety must be operated by another part of the brain.Dr.Youssef
Role of Tob gene in stress signaling is interesting. It can be likely used as a biomarker in the future to predict the vulnerability of individuals to stress.Dr.Swati Sharma, PhD
Researchers from OIST’s former Brain Mechanisms for Behavior Unit evaluated the function of the neurons in the hippocampus of the mice lacking the Tob gene. They found that excitation increased when inhibition decreased indicating a change in overall balance, which would have an impact on the behavior of the mouse. Eventually, scientists performed genetic studies, after subjecting mice to stress.
They found that stress will not alter the expression immediately. There were changes after 15 minutes after the mice were exposed to the stress. If the Tob gene is deleted there is an impact on other proteins and genes. Suggesting that there are several indirect and direct impacts of the Tob gene.
Dr. Youssef said, “Unmasking this function of the Tob gene in fear, depression, and anxiety could have great significance in formulating therapeutics for psychiatric stress.”