A novel N-acetyltransferase, Shati/Nat8l, was identified in the brains of mice exposed to methamphetamine. Shati/Nat8l overexpression in the medial prefrontal cortex (mPFC) was found to attenuate methamphetamine-induced dependence. The mPFC is a brain region that plays an important role in cognitive function. However, the effect of Shati/Nat8l on cognition and memory has not yet been clarified. To understand the role of Shati/Nat8l in memory, we generated C57BL/6J mice with overexpressed Shati/Nat8l in the mPFC and performed memory-related experiments, including novel object-location and object-in-context tests. Furthermore, we used quantitative immunohistochemistry to assess the presynaptic and postsynaptic proteins, synaptophysin and postsynaptic density protein (PSD)-95, respectively. Shati/Nat8l overexpression in the mPFC impaired both novel object-location and object-in-context memory. Moreover, Shati/Nat8l overexpression in the mPFC reduced PSD-95 levels, but not synaptophysin levels in the mPFC. These results demonstrated that Shati/Nat8l overexpression in the mPFC is involved in location and contextual memory, and can affect the excitatory postsynaptic protein, PSD-95.

一本小说N-乙酰转移酶 Shati/Nat8l 在暴露于甲基苯丙胺的小鼠的大脑中被鉴定出来。发现内侧前额叶皮层 (mPFC) 中的 Shati/Nat8l 过表达可减轻甲基苯丙胺诱导的依赖性。mPFC 是一个在认知功能中起着重要作用的大脑区域。然而，Shati/Nat8l 对认知和记忆的影响尚未阐明。为了了解 Shati/Nat8l 在记忆中的作用，我们生成了在 mPFC 中过度表达 Shati/Nat8l 的 C57BL/6J 小鼠，并进行了与记忆相关的实验，包括新的对象定位和上下文中的对象测试。此外，我们使用定量免疫组织化学分别评估突触前和突触后蛋白、突触素和突触后密度蛋白 (PSD)-95。mPFC 中的 Shati/Nat8l 过度表达损害了新的对象定位和对象上下文记忆。此外，mPFC 中的 Shati/Nat8l 过表达降低了 PSD-95 水平，但不会降低 mPFC 中的突触素水平。这些结果表明 mPFC 中的 Shati/Nat8l 过表达与位置和上下文记忆有关，并且可以影响兴奋性突触后蛋白 PSD-95。