NIH Research Festival
FARE Award Winner
Schizophrenia is a chronic brain disorder that affects ~ 1% of general population. Genetic studies have identified substantial numbers of susceptibility genes, however the pathophysiology of schizophrenia is still unclear and current pharmacological treatments offered limited success, especially for improving negative and cognitive symptoms. Unraveling pathological mechanisms of schizophrenia is critical for developing effective therapeutic strategies. Dysbindin (DTNBP1) is one of the earliest identified susceptibility genes. Genetic variations of Dysbindin have been well replicated as genetic risks associated with schizophrenia, and reduced dysbindin expression has been found common in brain areas of schizophrenia patients. To illustrate the mechanism of Dysbindin on brain function, we injected AAV1-Cre-eGFP virus into the prefrontal cortex (PFC) of Dysbindin conditional knockout mice, a well-established brain region for its involvement in cognition and schizophrenia. We found that Cre virus injection led to loss of Dysbindin expression in neurons of PFC. We then analyzed synaptic transmissions and behavior of mice injected with virus. We found that loss of Dysbindin significantly shifted excitation/inhibition balance toward hyperexcitation in PFC compared with that of wild-type mice. Deletion of Dysbindin in PFC also disrupted behavior of those mice. These results showed the important role of Dysbindin in synaptic activities and functions of PFC.
Scientific Focus Area: Neuroscience
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