Okinawa (Japan): The Tob gene, which was initially discovered in Prof. Tadashi Yamamoto's old group in Japan in 1996, is well known for its connection to cancer. Previous studies have shown that it also plays a role in controlling the cell cycle and the immunological response of the body. Now, scientists from the Okinawa Institute of Science and Technology (OIST) have discovered that this gene also has a significant role in lowering depression, fear, and anxiety in a multidisciplinary study that blends molecular biology with neuroscience. The Translational Psychiatry journal published their research.
Lead author Dr Mohieldin Youssef, a former PhD candidate in Prof. Yamamoto's Cell Signal Unit at OIST, stated that the study focused on understanding stress resilience. The gene contributes to stress resilience when it is present, while depression, fear, and anxiety rise when it is not. 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 exposed to a stimulus. According to Dr Youssef, because the gene responds so quickly, it has been classified 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 hypothesised before, this study is the first to prove that Tob protects the brain from stress.
Multiple tests led them to the conclusion that this gene is associated with anxiety, fear, and sadness. First, the scientists placed mice under stress, and as predicted, the levels of Tob protein rose. When they employed mice that were born lacking the Tob gene, they discovered an increase in depressive, phobic, and anxious behaviour. 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. Additionally, the mice lacking the Tob gene 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 realise that it isn't all that horrible and cease being scared. But even after several days, those lacking the Tob gene continued to exhibit elevated levels of fear manifested as frozen.
The scientists 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. The scientists then made the decision to focus on the gene's precise function within the hippocampus.
Injecting the Tob gene into the hippocampus of mice lacking the Tob gene while leaving it dormant in other bodily regions. The mice's despair and terror levels returned to normal, but their anxiety levels remained elevated. The scientists then performed the exact opposite, breeding a mouse that lacked the Tob gene in the hippocampus but had it in the rest of its body. 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.
The performance of the neurons in the hippocampus of the mice lacking the Tob gene was then evaluated by researchers from OIST's old Brain Mechanisms for Behavior Unit. 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 behaviour.
Finally, after subjecting the mice to stress, the researchers performed genetic studies. It's interesting that they discovered that stress didn't immediately alter facial expressions. However, there were alterations 15 minutes after the mice were stressed. If the Tob gene was deleted, it had an effect on other genes and proteins. This shows that the Tob gene probably has several direct and indirect effects.
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. —ANI