Isn’t it true that brain cells don’t divide, that when they die, they can’t be replaced?
SONG: Many people believed that for a long time, but around 20 years ago, researchers discovered stem cells in the brain. This source of these stem cells remains with people during most of their adult life.
Are these spread throughout the brain?
SONG: Unfortunately, they aren’t. If they were, we would probably be able to naturally heal every assault against our brains. There is a reservoir of stem cells found in the hippocampus—a part of the brain involved in learning, memory, information processing and mood regulation.
What are these stem cells doing?
SONG: We think these stem cells update the brain, similar to how a computer gets updated. When a computer becomes outdated, it runs slower and has less memory. But a computer can be upgraded by adding additional programs, memory and storage to make it run faster. Essentially, we think these stem cells swap in more RAM to keep the brain running in top shape. It’s interesting because we may have inadvertently been promoting brain stem cell upgrades in our treatments for mental disorders, like depression and bipolar disorder.
SONG: Research by us and other labs has shown that all the antidepressants used in the clinic, including drugs and electroconvulsive therapy, cause stem cells in the brain to divide more and make more neurons in mice. Now we found evidence that these stem cells may be responsible for decreasing depression by making more neurons that can form more connections in the brain. Exercise actually has a similar effect by stimulating the growth of more neurons, which in turn helps treat depression.
Do you think that having slowly dividing stem cells actually causes depression or other mental disorders?
In part. There‘s evidence that specific genetic changes in people with schizophrenia slow down the speed at which their stem cells divide to make new neurons. Through drug treatments, the patient’s stem cells can be stimulated to make more neurons.
But we do not know yet whether the disease and the slow division of the stem cells repairing the disease are a direct result of one another, or whether making new neurons compensates for another unrelated problem.
What work are you doing now in this area?
Since increasing the rate at which the brain’s stem cells divide seems to help treat depression and anxiety in both animals and people, we are testing new molecules in animals that activate stem cells and may be able to act as antidepressants in people.
We also know that certain antidepressants, like Prozac, work faster in some people than in others, and we believe that genetics plays a role in how you will respond to a medication. People with certain variations in their DNA may be more or less likely to respond to certain antidepressant treatments. We would like to find out what these variations are so we can predict whether a treatment will work for a particular patient.
Another project we are working on is learning how we can exploit these stem cells to treat brain injury or stroke. After a significant brain injury, the stem cells do make neurons that travel to the site of injury, but these new neurons eventually die, and we don’t know why. If we are ever going to be able to use these cells in therapies, we need to learn what is going on here in detail and how to keep the cells alive.
--Interviewed by Vanessa McMains
Hongjun Song on using stem cells in the brain to study mental disorders:
Video transcription: "My lab works on stem cells in the nervous system. In particular, we look at how stem cells are regulated in the adult brain in the region called the hippocampus. This is a region involved in learning and memory and mood regulation. So we try to understand how actually these stem cells are activated and how they are regulated, or how they are dysregulated in mental disorders. We’re very interested in adult neural stem cells for a couple of reasons. One of them is it is generally believed that the adult brain is a very inhibitory environment for mature neurons. That is why during an injury, old neurons cannot regrow. However, these young neurons actually have an amazing capacity to regrow, reconnect and contribute to the circuitry. We want to know how actually they do that, how the young cells can connect to the circuitry and contribute to the brain functions. We also want to know how the local environment, in this particular case, actually can support that growth. How they can take upon those new neurons and make them useful. We hope is that by learning how they do it, we can use this strategy to promote regeneration of the mature brain in the other part where we do not have stem cells and to promote regeneration of mature neurons after injury.
"It turns out that these stem cells are very good tools to study why genes involved in mental disorder lead to defects in neurodevelopment. We’re also using this as a model system in rodents to study how a gene implicated in mental disorders, such as depression and schizophrenia, how do they affect the development of new neurons in the adult brain. At the same time, once we identify a specific defect caused by some genes involved in neurodevelopment, we actually can go back to human genetics to try to understand whether these are new genes involved in schizophrenia or depression or bipolar disorders."