Project Summary

Steven E. Arnold, M.D., (Independent Investigator 2006) of the University of Pennsylvania, aims to study in the “sandy” animal model the role of stress in precipitating the first episode of schizophrenia and subsequent relapse in vulnerable individuals. Recently, many genes have been identified associated with schizophrenia, but how these genes interact with the environment, such as stressful situations, remains an open question. Among the specific genes linked to schizophrenia, dysbindin (ex. DTNBP1), a newly characterized protein, is the most highly replicated so far, with at least 18 significant associations reported in populations around the world. Dysbindin is expressed in neurons and some synapses throughout the brain. Dr. Arnold has found significant decreases in dysbindin protein expression in glutamatergic presynaptic terminal fields in the hippocampus in postmortem brain tissues of schizophrenic patients. His preliminary immunohistochemical, biochemical, ultrastructural, and neurophysiological data in humans, mice, and the dysbindin-mutant mouse "sandy" indicate dysbindin plays an important role in synaptic functioning. But almost nothing is known about behavior in the sandy mouse. What happens to behavior and synaptic integrity in chronically stressed mice with a functional dysbindin mutation? This proposal aims to investigate how memory, locomotor, exploratory and social behaviors are affected in sandy mice that undergo early life and chronic stress. He hypothesizes greater abnormalities in behavior and synaptic integrity in stressed sandy mice compared to stressed and non-stressed control mice.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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