D-serine, a stimulator of activity at certain types of receptors in brain cells, has been tested as a new type of treatment for schizophrenia and bipolar disorder. Recently published research suggests it may be important for building up the brain circuitry that helps people filter out unnecessary information. According to a study in the May 26th issue of Molecular Psychiatry, the findings could help scientists learn whether a lack of D-serine in newborns might lead to schizophrenia symptoms in adulthood.

In the new study, Johns Hopkins University School of Medicine scientist Akira Sawa, M.D., Ph.D., (2002 and 2004 NARSAD Young Investigator, 2011 NARSAD Distinguished Investigator grantee, and Scientific Council member), and his colleagues looked at mice that were altered genetically to produce low levels of D-serine during the neonatal (newborn) stage. D-serine helps activate NMDA receptors, communication ports found on excitatory neurons. NMDA receptors are known to be involved in changing neural connections as the brain learns and creates memories. Scientists theorize that some schizophrenia symptoms may arise when these receptors are blocked from working or work only weakly.

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Dr. Sawa and his colleagues found that adult mice that developmentally displayed low levels of D-serine performed differently than healthy mice in a series of behavior experiments. The mice performed worse on some memory tests and tests of the brain’s ability to filter out distracting information. The low levels of D-serine in these mice also altered the way that certain neurons fired in response to NMDA receptor signals. The researchers could correct these abnormalities in newborn mice by injecting them with regular D-serine treatments in the neonatal stage. However, a similar treatment given to the animals during their adulthood did not correct these problems.

The scientists suggest that a shortage of D-serine might reduce the activity of NMDA receptors in newborn mice, which in turn could prevent their brains from building up important neural connections that control some of the behaviors seen in schizophrenia and perhaps other disorders.

From Johns Hopkins, the scientific team also included a number of past NARSAD grantees: Young Investigator grantees Hanna Jaaro-Peled, Ph.D., and Atsushi Kamiya, M.D., Ph.D.; Distinguished Investigator grantee Richard Huganir, Ph.D.; and Independent Investigator grantee Mikhail V. Pletnikov, M.D., Ph.D. University of Maryland School of Medicine researcher and Scientific Council member Patricio O'Donnell, M.D., Ph.D., who has received Young Investigator, Independent Investigator, and Distinguished Investigator grants, was also a co-author of the study.

Read the abstract.