A genetic mutation found in two human patients with schizophrenia Researchers at the University of Illinois Urbana-Champaign and Colleagues in Massachusetts and Germany. Their paper is Published in Molecular psychiatry,

The Mutation Increases Levels of Glycine Decarboxylase, or GLDC, An Enzyme Responsible for registered glycine in the brain. Glycine Activates receptors for the neurotransmitter glutamate, Called NMDA receptors.

“The genetics of schizophrenia is very complex, and it is rare that mutations found in patients can be linked directed directly to the disease,” said Study Leader Uwe Rudolph, A Professor of Compactive Biosciences at Illinois.

“Schizophrenia is not annoded by any kind of lab test or imaging; it’s stil a clinical diagnosis based on symptoms. The hope is that these kinds of rare mutations COLLD LEAD Us to the BioCal and Physiological pathways that are important to study. “

The study began when a genetic mutation was found in two schizophrenia at MCLEAN HRSPITAL in Belmont, mass. They have multiplied copies of a section of dna that include the gene for GLDC. Curious as to whather the mutation contributed to their Symptoms, The MCLEAN TEAM Studying The Patients Reached Out to Rudolph’s lab to create a line of Mice with the Same Mutation.

The Mice With Mutations analogous to that in the human patients To further narrow down the genetic link, the resultars next developed lines of Mice with Multiple Copies of only a more a less genes contained within the larger segment repaired in the sings, then a single Gene: GLDC.

“We found that Extra Copies of the Gldc Gene Alone Were Suficynt to render the schizophrenia-like behaviors we had observed,” said rudolph, who also isfiliated with the neuroscience Program and the Carl R. Woese Institute for Genomic Biology at Illinois.

To undersrstand why multipliple copies of the Goldc Gene Bold Be Solely Responsible For the Behavioral Symptoms, The Researchers Took A Closer Look at What was Happening in the Brains of the MICE, SPACIFICLOLY TODE Levels of Glycine and the Function of NMDA receptors.

“We hypotesized that extra copies of Gldc would result in a lower level of glycine in the brain, since it degrades glycine. Acnce the there is no enough GLYCINE to All the Activate the NMDA Receptors, “said Illinois postdoctoral Researcher Maltesh Kambali, The First Author of the Paper. “We Measure an increase in activity of the Gldc Enzyme in the Brains of our Mice, which would point to that as well.”

However, when the resarchers measured glycine levels in the brains of their mice, there did not see seem to be a significant different difference between those that with the entra gldcc and healthy message. So rudolph’s team turned to colleagues in Germany who had developed sophisticated methods of tracking glycine in the brain.

The German Team Found That, While The Overall Amount of Glycine in the Whole Brain was Similar, The Amount of Glycine Outside of the NERVE CELLS and Available to Hell to Hell to Hell to Hell Lower in a Subregion of the Hippocampus in the Mice With Multiple Copies of Goldc.

To see why this region of the brain was so affected, rudolph’s team then worked with resarchers at Harvard Medical School to Perform Functional Studies on the Affected Brain SIBREGION SIBREGION SIBREGION, Called the Dentate Gyrus. They identified decreased activity in the neural synapses, the active Junctions that Send Signals Between Neurons. They Pinpointed Differences in Long-Term Potentiation, A Sustained Strengthaning of Activity in the Synapse during the Learning Process.

“We saw how glycine measurements and the long-term poteniation measurements were showing converging changes in this dentate gyrus region, but not in other regions of the hippoc Development of psychosis to the activity in the dentate gyrus. So our findings fit with that theory, “kambali said.

The Illinois Team then Conducted A Biochemical Analysis of the Dentate Gyrus in the Mice With Extra Copies of GLDC. They found that some pathways previously implicated in schizophrenia had reduced activity, indicating that the increase in GLDC and Associate Decrease of Glycine was indeed Subeciate to inhibit NMDA receptors’ function and was involved in the schizophrenia symptoms they hand observed.

“This study demonstrated at multiple levels how GLDC Functions as a Novel Regulator of Nmda Receptors,” Rudolph said. “Dysfunction of nmda receptors have been shown to be important in the pathophysiology of schizophrenia. Yet this finding is also related independently of dies Essential for many brain functions, including learning and memory. “

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