• Kyosuke Uno, Hajime Miyanishi, Kengo Sodeyama, Toshiyuki Fujiwara, Toh Miyazaki, MuramatsuShin-IchiSIDivision of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan; Center for Gene & Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan., and Atsumi Nitta.
• Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan; Laboratory of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Japan.
• Behav. Brain Res. 2019 Dec 30; 376: 112227.

AbstractThe number of patients with depressive disorders is increasing. However, the mechanism of depression onsets has not been completely revealed. We previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. In this study, we revealed the involvement of Shati/Nat8l in the vulnerability to major depression. Shati/Nat8l mRNA was increased only in the striatum of mice, which were exposed to chronic social defeat stress. Shati/Nat8l-overexpressed mice showed impairment in social interaction and sucrose preference after the subthreshold social defeat (microdefeat) stress. These depression-like behaviors were restored by fluvoxamine and LY341495 injection prior to these tests. Furthermore, the intracerebral administration of only fluvoxamine, but not of LY341495, to the dorsal striatum and direct infusion of LY341495 to the dorsal raphe also rescued. Taken together, Shati/Nat8l in the striatum has an important role in the vulnerability to depression onsets by regulating the origin of serotonergic neuronal system via GABAergic projection neuron in the dorsal raphe from the dorsal striatum.Copyright © 2019 Elsevier B.V. All rights reserved.

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