Vulnerability to depressive behavior induced by overexpression of striatal Shati/Nat8l via the serotonergic neuronal pathway in mice
Vulnerability to depressive behavior induced by overexpression of striatal Shati/Nat8l via the serotonergic neuronal pathway in mice
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DOI：
10.1016/j.bbr.2019.112227
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发表时间：
2019-12
影响因子：
2.7
通讯作者：
K. Uno;Hajime Miyanishi;Kengo Sodeyama;Toshiyuki Fujiwara;Toh Miyazaki;S. Muramatsu;A. Nitta
中科院分区：
文献类型：
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作者：
K. Uno;Hajime Miyanishi;Kengo Sodeyama;Toshiyuki Fujiwara;Toh Miyazaki;S. Muramatsu;A. Nitta
患有抑郁症的患者数量正在增加。然而，抑郁症发病的机制尚未完全揭示。我们之前使用精神病动物模型在大脑中发现了 Shati/Nat8l（一种 N-乙酰转移酶）。在这项研究中，我们揭示了 Shati/Nat8l 与重度抑郁症易感性的关系。 Shati/Nat8l mRNA 仅在暴露于慢性社交失败压力的小鼠纹状体中增加。 Shati/Nat8l 过表达的小鼠在阈下社交失败（微失败）压力后表现出社交互动和蔗糖偏好受损。在这些测试之前，通过注射氟伏沙明和 LY341495 可以恢复这些抑郁样行为。此外，仅脑内给予氟伏沙明，而不是LY341495，至背侧纹状体，以及直接将LY341495输注至中缝背侧，也可以挽救病情。总而言之，纹状体中的 Shati/Nat8l 通过通过来自背侧纹状体的中缝背侧的 GABA 能投射神经元调节血清素能神经元系统的起源，在抑郁症发作的脆弱性中发挥重要作用。
The number of patients with depressive disorders is increasing. However, the mechanism of depression onsets has not been completely revealed. We previously identified Shati/Nat8l, anN-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 systemviaGABAergic projection neuron in the dorsal raphe from the dorsal striatum.