[Background] The number of patients that have depressive disorder is increasing. However, the mechanism of depression onsets has not been completely revealed. We have previously identified Shati/Nat8l (Shati), an N-acetyltransferase, in the brain using a mouse model of psychosis. We reported that Shati is related to developmental disorder and methamphetamine dependence. In this study, we revealed the involvement of Shati in the vulnerability of major depression.
[Methods] We generated the Shati-overexpressed mice by injecting an adeno-associated virus into the dorsal striatum, followed by exposed the subthreshold micro social defeat stress (MSDS).
[Results] Shati-overexpressed mice showed the impairment of social interaction and sucrose preference after the MSDS. These depression-like behaviors were restored by fluvoxamine and LY341495 injection prior these tests. Furthermore, the intracerebral administration of fluvoxamine restored.
[Conclusions] Taken together, Shati in the striatum has an important role in the vulnerability of depression onsets by regulating serotonergic neuronal system. Our study suggested the new pathways induce depression like-behaviors, and Shati in the striatum might be a new target for medical tools for depression.
