As the highest part of the nervous system and the most developed thinking organ, the brain dominates all activities in the body and regulates the balance between the body and the surrounding environment, which is the material basis of higher nervous activities. Tofu-like brain is quite fragile, extremely fragile. Do adults repair themselves when their brains are damaged? How to fix it? This is a basic problem that scientists have been trying to figure out.

Scientists from the Department of Brain Science, School of Medicine, University of California, San Diego, published a new discovery in Nature the day before yesterday, saying that when brain cells are injured in adulthood, they will return to embryonic state. Scientists report that after brain injury, cells can regenerate new connections under immature adaptation, which helps to restore lost functions under appropriate conditions.

Repairing brain and spinal cord injuries is the most difficult challenge in the medical field. Until recently, this seemed an impossible task. This new study proposes a "transcription roadmap for regeneration".

Transcription refers to the process of copying genetic information from DNA to RNA (especially mRNA) under the catalysis of RNA polymerase. Transcription, as the first step in protein biosynthesis, is the way to synthesize mRNA and noncoding RNA(tRNA, rRNA, etc.). ).

Mark Tuszynski, the main author of the paper, a professor of neuroscience at the University of California, San Diego and director of the Institute of Translational Neuroscience, said, "With incredible tools such as modern neuroscience, molecular genetics, virology and computing power, we can identify for the first time how the entire genome in adult brain cells resets itself to regenerate, which makes us know how to regenerate at the transcription level."

Through the mouse model, the research team found that the mature neurons in the adult brain will return to the embryonic state after being damaged. Tusinschi said. "Who would have thought that only 20 years ago, we regarded the adult brain as static, undifferentiated, completely established and unchangeable."

In the past, researchers have found that the hippocampus and subventricular zone constantly produce new brain cells, which replenish these brain regions throughout their lives. Tusinschi said: "This research work has further strengthened this concept." "The brain's ability to repair or replace itself is not limited to these two areas. On the contrary, when adult brain cells in adult cerebral cortex are damaged, they will return to embryonic cortical neurons at the transcription level. If it is immature, it can regrow nerve axons and provide an environment for growth. In my opinion, this is the most striking feature of this study, which is shocking. "

The transverse section of the rat brain shown in the figure below shows that the cells (blue) with normal Huntington gene expression return to the initial state after damage, while the genes of the cells (red) without Huntington gene are eliminated, showing less regeneration.

Huntington protein gene, as shown in the figure below, is abbreviated as HTT gene. As a part of clinical research on Huntington's disease, the gene and its products are being widely studied, which may reveal the role of Huntington's protein in long-term memory storage.

In order to provide an "environment to encourage regeneration", scientists studied the response of injured neurons after spinal cord injury. In recent years, researchers have greatly improved the possibility of using transplanted neural stem cells to stimulate the repair and recovery of spinal cord injury, mainly by inducing neurons to make axons pass through and through the injured site and reconnect the severed nerves.

For example, last year, this interdisciplinary research team described the use of 3D printed implants to promote the growth, restoration of connectivity and functional loss of nerve cells in spinal cord injury in rats.

The latest research has produced a second surprise: in promoting the growth and repair of neurons, an essential genetic pathway involves Huntington's gene, which will lead to Huntington's disease after mutation, which is a destructive disease characterized by the gradual failure of brain cells.

The research team found that the "regenerative transcriptome" of messenger RNA molecules used by cortical spinal cord neurons was maintained by Huntington gene. In genetically engineered mice lacking Huntington gene, spinal cord injury showed that the germination and regeneration of neurons were significantly reduced.

Tuschinski said: "Although a lot of work has been done to understand why Huntington gene mutation causes diseases, people still know little about the normal function of Huntington gene." "Our work shows that Huntington protein is very important for promoting the repair of brain neurons. Therefore, the mutation of this gene is expected to lead to the loss of self-repair ability of adult neurons. This in turn may lead to chronic neuronal degeneration, which may lead to Huntington's disease. "