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Editor's Note: The following article is part of an ongoing science series written by Arkansas State University faculty members and published periodically by The Sun.

By Malathi Srivatsan

We all understand what a skin scar is. However it is hard to imagine that something similar to a "scar" can form in the brains of people.

We all know that skin scars develop because of lesions in skin. However, Dr. Eric Nestler and his research associates from the University of Texas Southwestern Medical Center in Dallas, report that a "molecular scar" can form in a brain wounded by repeated experiences of hurt and failure in life, often resulting in depression. No wonder depression is hard to cure.

But how does a feeling of defeat gets converted to a molecular scar?

The answer appears to be in a molecule that is made in large quantities during development in our brain. The name of this chemical is the Brain Derived Neurotrophic Factor or BDNF.

In the developing fetal brain, BDNF works like brain fertilizer. In its presence brain cells known as neurons sprout large number of branches and extend them rapidly to make new connections. While BDNF promotes growth of neurons in the fetus, in the adult brain it helps to promote function by increasing the release of brain chemicals called neurotransmitters.

The release and presence of appropriate levels of neurotransmitters, achieved in part by BDNF, is important for a healthy brain and a self-confident, cheerful personality. In contrast, an imbalance of neurotransmitters called dopamine and norepinepherine in the brain results in depression and a feeling of worthlessness. During depression the brain makes less BDNF.

Dr. Nestler's research group induced a depression-like condition in mice by exposing them to social stress. They placed the mice in the cage with more dominant mice that bullied them. Eventually the "defeated" mice started avoiding all other mice and went into a mood of depression. In addition to the social withdrawal, repeated defeat left mice with a long lasting "molecular scar" a condition in which "silencer molecules" turn off the gene that makes BDNF. What are these silencer molecules?

The "silencer molecules" are chemicals that turn off genes by attaching themselves to other chemicals which are wrapped together with DNA. The histone- DNA interaction silences the ability of the genes to produce BDNF. The fact that a reduction in BDNF is associated with depression is further supported by the finding that certain anti depressants such as impramine temporarily elevates the levels of BDNF in the brain.

Anti-depressants do not remove the scar. However they can make chemical activators attach to DNA and overcome the silencer chemicals. That is how when mice were given an antidepressant, impramine, it temporarily restored BDNF production. Since impramine did not remove the molecular scar, it shows how long lasting are the adverse changes induced by chronic stress on brain function.

Is there a long lasting solution to overcome the silencer molecules?

Recent findings show that regular physical exercise increases the levels of BDNF in the brain. Dr. Fred H. Gage of the Salk Institute in La Jolla, Calif., and his associates studied two groups of healthy rats; one group had running wheels and exercised regularly.

When they dissected the rats' brains, Gage's team found that the runners had more new neurons and stronger connectivity. These researchers also found that the exercised rats had higher activity in the gene involved in the production of BDNF. It is only natural that physical activity is linked to better brain function since animals use their brains while they move to find food and run away from predators.

I am currently studying the mechanisms of molecules in the nervous system similar to BDNF that provide protection to the nervous tissue.

Thus, in addition to making us look good, exercise benefits our brains by increasing the production of BDNF.

For more information contact the ASU Dept. of Biological Sciences at biology@astate.edu.

Dr. Malathi Srivatsan is an assistant professor of biology at Arkansas State University