Stony Brook, NY; Stony Brook University: Assistant Professor in the School of Medicine's Pharmacological Sciences Department Adan Aguirre, PhD (Front left) with members of his team Jianchos Gao (center front), Nadia McMillan (Right Front) and (rear Left to right) Michael Klingener, Dr. Javier Palazuelos, Manideep Chavali, and Israa Hussein with a projected image of a rare type of glial cells, called NG2 glia.

Members of a research team led by Adan Aguirre, an assistant professor in the School of Medicine’s Pharmacological Sciences Department, pose in front of a projected image of a rare type of glial cell called NG2 glia. In the front, from left, are Aguirre, Jianchos Gao and Nadia McMillan. In the rear, from left, are Michael Klingener, Javier Palazuelos, Manideep Chavali and Israa Hussein. PHOTO CREDIT: STONY BROOK UNIVERSITY

The human brain is composed two main groups of cells: neurons and glial cells. Neurons can be thought of as the highway of the brain; they are the structural basis the brain uses to send messages. Three different glial cell types exist in our brains: astrocytes, oligodendrocytes and microglia.

It has long been believed that the sole function of oligodendrocytes is the formation of myelin sheaths, fatty casings around neurons that promotes the conductivity of nerve impulses. This understanding of oligodendrocytes is beginning to change thanks to a recent Stony Brook University study.

A research team led by Adan Aguirre, Ph.D., an assistant professor in the Department of Pharmacological Sciences at Stony Brook University School of Medicine, discovered that a reduction in NG2 glia, precursor oligodendrocytes, can lead to depressive-like behaviors. This discovery, published in the journal Neuron, provides a deeper understanding of the purpose of oligodendrocytes and opens the door to novel treatment options for depression.

Aguirre has been studying glial cells for several years and was curious as to why oligodendrocytes could be found in regions of the brain where there is no need for myelin sheaths.

“What are these cells doing there when there is no myelin? Is there any other function that these cells achieve?” Aguirre said. “There must be a reason why those cells are there.”

To determine why oligodendrocytes might be in regions of the brain where they seem to serve no direct purpose, Aguirre focused on the precursor oligodendrocytes, NG2 glia. The first experiment conducted by the research team involved the use of genetic manipulations to ablate NG2 glia in adult mice. This process kills most of the NG2 glia in the brain and allowed the researchers to study what effect the reduction may have on the mouse’s behavior.

The researchers observed through the use of psychological tests that the mice with decreased NG2 glia in the prefrontal cortex presented depressive-like behaviors.

“We found that the mice with ablated NG2 glia in the prefrontal cortex exhibited depressive-like behavior,” Aguirre said. “The next step was, how are the cells regulating this behavior but also, what is the specificity of these cells in the prefrontal cortex compared to those in other parts of the brain.”

To determine how the NG2 glia in the prefrontal cortex was regulating depressive-like behavior, Aguirre used mice that are bred to exhibit these types of behavior. The brains of these mice were analyzed for both the number of NG2 glia in the prefrontal cortex as well as the genes that were being expressed by these cells.

The research team found that the mice exhibiting depressive-like behaviors had less NG2 glia and significantly less expression of the growth factor FGF2. This growth factor facilitates astrocytes to regulate glutamate, the main excitatory neurotransmitter in the brain.

The third experiment conducted by the researchers involved knocking out the NG2 glia gene for production of FGF2. This also resulted in the development of depressive-like behaviors in mice, further supporting the hypothesis that NG2 glia are instrumental in opposing depression.

“FGF2 disrupts glutamate transmission regulation, causing depression, and our findings open a new pathway for pharmaceutical development to treat depression,” Aguirre said. “In addition to this possibility, we also discovered that NG2 glia are involved in a function other than the production of myelin.”