Summer 2017

A New Hope

This just-discovered pathway in the brain may hold promise for improving schizophrenia treatment.

By David Levin

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Astrocytes (shown here in fluorescent green) link major brain receptors associated with learning and memory. Photo: Jaclyn Dunphy, Neuron

Life can be a constant struggle for patients with schizophrenia. The mental disorder can impair a person’s ability to manage emotions, make rational decisions and function socially. It can even blur the line between what’s imagined and what’s real, causing terrifying confusion.

A discovery by Tufts researchers may help change the way the disease is treated. In a paper published in Neuron in May, the team—led by Dr. Philip Haydon, director of Tufts Neuroscience Institute—revealed a previously unknown brain pathway that could be related to schizophrenia, opening the door for new treatments and therapeutic drugs. The researchers suggest that while most existing schizophrenia drugs act directly on neurons, targeting certain supporting brain cells—called astrocytes—might be more effective.

Neurons are responsible for memory, activity and learning. If they are the brain’s pro athletes, then astrocytes act as their coaches. While neurons send commands to one another hundreds of times per second, astrocytes take a big-picture approach, telling neurons how active they should be throughout the day. “Astrocytes act sort of like dimmer switches,” said Thomas Papouin, the paper’s lead author and a research assistant professor at Tufts School of Medicine. “They can turn neuronal activity up or down on a large scale.”

One of the ways astrocytes do this is by releasing a brain chemical called D-serine, though how the cells know when to release it—and in what quantities—was unclear until now. Papouin and his colleagues, including Jaclyn Dunphy, a Ph.D. candidate at the Sackler School, unraveled that mystery in their experiments. The group monitored D-serine levels in mice over time, finding that the levels appeared to rise and fall in concert with a molecule called acetylcholine. This chemical, they said, seems to trigger a response in astrocytes, prodding them to release D-serine, thereby regulating neuronal activity.

This could be good news for patients with schizophrenia, who have low levels of both acetylcholine and D-serine—deficits that may contribute to their disorder. “Giving schizophrenic patients D-serine directly can help counteract their symptoms, but can also cause serious kidney problems,” Dunphy said. “We think it might be better to manipulate D-serine levels in the brain by targeting astrocytes instead.”

Papouin said it may be years before this finding could be used to develop new medication—but the team is excited by the possibility. “It’s a step,” Papouin said. “We’ve found a relationship between two chemicals in the brain that are both implicated in schizophrenia, yet for a long time, were thought to be completely separate.”

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