Src deficient mice demonstrate behavioral and electrophysiological alterations relevant to psychiatric and developmental disease

Publication date: Available online 28 February 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Katelyn R. Ward, Robert E. Featherstone, Melissa J. Naschek, Olga Melnychenko, Anamika Banerjee, Janice Yi, Raymond L. Gifford, Karin E. Borgmann-Winter, Michael W. Salter, Chang-Gyu Hahn, Steven J. SiegelAbstractMuch evidence suggests that hypofunction of the N-methyl-d-aspartate glutamate receptor (NMDAR) may contribute broadly towards a subset of molecular, cognitive and behavioral abnormalities common among psychiatric and developmental diseases. However, little is known about the specific molecular changes that lead to NMDAR dysfunction. As such, personalized approaches to remediating NMDAR dysfunction based on a specific etiology remains a challenge. Sarcoma tyrosine kinase (Src) serves as a hub for multiple signaling mechanisms affecting GluN2 phosphorylation and can be disrupted by convergent alterations of various signaling pathways. We recently showed reduced Src signaling in post mortem tissue from schizophrenia patients, despite increased MK-801 binding and NMDA receptor complex expression in the postsynaptic density (PSD). These data suggest that Src dysregulation may be an important underlying mechanism responsible for reduced glutamate signaling. Despite this evidence for a central role of Src in NMDAR signaling, little is known about how reductions in Src activity might regulate phenotypic changes in cognition and behavior. As suc...

Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - February 28, 2019 Category: Psychiatry Source Type: research