McLean Hospital 115 Mill Street Belmont, MA 02478
For decades, scientists have known that gamma-aminobutyric acid (GABA) is a key factor in the development of neuropsychiatric disorders. But recent discoveries in the Angiogenesis and Brain Development Laboratory of Anju Vasudevan, PhD, have literally opened a new pathway.
Disruptions in prenatal brain development can lead to disorders such as epilepsy, autism, schizophrenia, and anxiety. The Vasudevan laboratory, established in 2011, investigates key events in that development, with the long-term goal of ensuring that early brain development remains on track.
Today, one in four people worldwide experience every year some form of neuropsychiatric illness, often the product of abnormal early brain development. Drugs currently used in psychiatry, however, only treat symptoms, as there is still a lack of insight into how these diseases develop.
Research has traditionally focused on GABA and its role in the prenatal development of neurons. But Vasudevan is looking at what she believes is the equally important development of blood vessels.
“Brain development is like a gem that is cut with many facets that sparkle,” she said. “What is new here is that we are saying there is an alternate GABA pathway in blood vessels, and If you disturb that pathway, this too results in neuropsychiatric disorders. It’s like two sides of a coin.”
GABA is a neurotransmitter that blocks impulses between nerve cells in the adult brain. But in the embryonic brain, its function is reversed, exciting impulses crucial to the development and maturation of nerves and serving as a key player in building the cortical network.
Working with experimental mouse models and using techniques involving developmental biology, genetics, cell biology, biochemistry, and imaging, Vasudevan’s lab discovered that angiogenesis (development of blood vessels), also plays a role in the development of nervous system disorders.
By deleting genetic components from endothelial cells that transport and receive GABA in the developing blood vessels, Vasudevan’s team discovered “a whole new perspective for the disease itself,” she said, explaining that when these genes are deleted, blood vessels don’t form normally prenatally and in turn, disturb the development of neurons.
Angiogenesis drugs now commonly used clinically for diseases such as heart attacks and strokes could eventually play a role in the prenatal stages to “rescue” blood vessel development and “restore the postnatal behavior,” she said.
“We have medications to delay strokes or to protect against strokes or heart attacks, but we have not thought of that perspective when it comes to psychiatric diseases. By tapping into the right gene pool, we can use angiogenesis to prevent or treat psychiatric disorders.”
Vasudevan estimated that her lab may be two to three years away from producing the laboratory results needed in mice before transitioning to research that could impact humans. Such clinical research would likely involve a test to determine the potential impact on postnatal treatment.
In addition, Vasudevan and her group study embryonic brain endothelial cells in depth. These have considerable potential for intervening in the adult brain to bring about positive outcomes for repair and regeneration of new brain cells.
“The potential of embryonic cells is that they are better at everything,” she said. “They are more plastic, they can proliferate more, they can migrate better. These are characteristics that are lost in the adult brain. When you look at children, they learn faster. As you get older, it gets more difficult to learn new stuff. You lose that plasticity. Embryonic cells have a lot of potential if used correctly in the right scenario. They can serve as a great means for repair and regeneration.”