Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan; Laboratory Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan.
Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Biochem Biophys Res Commun. 2024 Dec 3;736:150435. doi: 10.1016/j.bbrc.2024.150435. Epub 2024 Jul 22.
Shati/Nat8l was identified as an upregulated molecule in the nucleus accumbens (NAc) of mice following repeated methamphetamine administration. Region-specific roles of this molecule are associated with psychiatric disorders. In the present study, we examined the importance of Shati/Nat8l in the hippocampus because of its high expression in this region. Mice with a hippocampus-specific knockdown of Shati/Nat8l (hippocampal Shati-cKD) were prepared by the microinjection of adeno-associated virus (AAV) vectors carrying Cre into the hippocampus of Shati/Nat8l mice, and their phenotypes were investigated. Drastic reduction in the expression and function of Shati/Nat8l in the hippocampus was observed in Shati-cKD mice. These mice exhibited cognitive dysfunction in behavioral experiments and impaired the electrophysiological response to the stimuli, which elicits long-term potentiation. Shati/Nat8l in the hippocampus is suggested to possibly play an important role in synaptic plasticity to maintain cognitive function. This molecule could be a therapeutic target for hippocampus-related disorders such as dementia.
沙提/Nat8l 被鉴定为反复给予安非他命后，老鼠伏隔核（NAc）中上调的分子。该分子的区域特异性作用与精神疾病有关。在本研究中，由于其在该区域的高表达，我们检查了 Shati/Nat8l 在海马体中的重要性。通过将携带 Cre 的腺相关病毒（AAV）载体注入 Shati/Nat8l 小鼠的海马体，制备了具有海马体特异性 Shati/Nat8l 敲低（海马体 Shati-cKD）的小鼠，并对其表型进行了研究。在 Shati-cKD 小鼠中观察到 Shati/Nat8l 在海马体中的表达和功能明显降低。这些小鼠在行为实验中表现出认知功能障碍，并损害了对引发长时程增强的刺激的电生理反应。提示海马体中的 Shati/Nat8l 可能在维持认知功能的突触可塑性中发挥重要作用。该分子可能是与海马体相关的疾病（如痴呆）的治疗靶点。
