Researchers Uncover Clue to Brain Abnormalities in Schizophrenia

What they did: A team of scientists including NYSCF Scientific Advisor and Harvard University Professor of Stem Cell and Regenerative Biology Dr. Kevin Eggan and NYSCF Research Institute Senior Principal Investigator Dr. Valentina Fossati have used stem cells to assess the role of a type of brain cell called oligodendrocytes in patients with schizophrenia.

What they found: The team found that patients with schizophrenia tended to produce fewer oligodendrocytes than those without the disorder, potentially leading to issues with connectivity and signaling within the brain.

Why it matters: Investigating the role of oligodendrocytes in schizophrenia will help scientists better understand the cellular basis of the disease and develop new treatments.

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One of the hallmarks of schizophrenia pathology is poor brain connectivity— basically, that the brain has a hard time sending and receiving signals. The substance that helps our brains send signals is called myelin – a fatty protein that coats our nerve fibers. Myelin is made by brain cells called oligodendrocytes, and when these cells die or malfunction, signaling gets harder.

A team of scientists – including NYSCF Scientific Advisor and Harvard University Professor of Stem Cell and Regenerative Biology Dr. Kevin Eggan and NYSCF Research Institute Senior Research Investigator Dr. Valentina Fossati – decided to investigate whether oligodendrocyte irregularities could be occurring in the brains of patients with schizophrenia, potentially leading to the connectivity and signaling issues we see in the disorder.

To address this question, the researchers took samples of skin cells from six patients with schizophrenia and six healthy controls, converted those cells into induced pluripotent stem cells, and then turned those stem cells into oligodendrocytes, which they studied for abnormalities. The team then took MRIs of each subject’s brain and observed the amount of white matter (the pale tissue of the brain made from nerve fibers and myelin) in each.

After checking in on the number of oligodendrocytes produced from each subject after 65, 75, and 85 days, the team found that patients with schizophrenia consistently generated fewer of the myelin-producing oligodendrocytes than healthy controls. Moreover, what was happening in the lab was mimicked in the brain: patients with schizophrenia had a decreased amount of white matter, correlating with the depletion of oligodendrocytes in the dish.

This study is important because it suggests that oligodendrocytes and myelination play a role in schizophrenia pathology, giving scientists a new target for therapeutics. Encouraging oligodendrocyte development or stimulating their activity could help increase brain signaling and relieve symptoms of the disorder: this promising new avenue for treatment will be further explored in future studies.

Diseases & Conditions:

Development, Neurobiology

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