Vascular dementia (VaD) is the second most common subtype of dementia, but the precise mechanism underlying VaD is not fully understood. Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can act as a key regulator in physiological and pathological processes, including neurological disorders, but whether it is correlated with VaD has not been elucidated. In this study, we established a mouse model of VaD by the transient bilateral common carotid artery occlusion surgery. As expected, the Morris water maze showed that VaD mice had significant deficits in spatial learning and memory. MALAT1 was elevated in the hippocampus of VaD mice. Additionally, we found that microRNA (miR)-9-3p was downregulated in the VaD hippocampus. By performing a dual-luciferase report assay, we verified the binding relationship between MALAT1 and miR-9-3p. Interestingly, synapse-associated protein-97 (SAP97), a well-known gene related to synaptic functions, was found upregulated in the hippocampus of VaD mice. In vitro experiments performed on hippocampal neurons demonstrated that miR-9-3p negatively regulated SAP97 expression. The downregulation of MALAT1 in hippocampal neurons increased miR-9-3p and reduced SAP97, whereas miR-9-3p inhibition rescued the MALAT1 downregulation-mediated SAP97 reduction. In conclusion, the present study reported the alterations in the expression levels of MALAT1, miR-9-3p, and SAP97 in the hippocampus of VaD mice, suggesting that MALAT1 targets miR-9-3p to upregulate SAP97 in the hippocampus of mice with VaD. This work will be helpful for understanding the molecular mechanisms of VaD.

血管性痴呆 (VaD) 是第二常见的痴呆亚型，但 VaD 的确切机制尚不完全清楚。长非编码RNA（lncRNA）转移相关肺腺癌转录物1（MALAT1）可以作为生理和病理过程（包括神经系统疾病）的关键调节因子，但其是否与VaD相关尚未阐明。在本研究中，我们通过短暂性双侧颈总动脉闭塞手术建立了VaD小鼠模型。正如预期的那样，Morris 水迷宫显示 VaD 小鼠在空间学习和记忆方面存在显着缺陷。VaD 小鼠海马体中 MALAT1 升高。此外，我们发现 microRNA (miR)-9-3p 在 VaD 海马中下调。通过进行双荧光素酶报告测定，我们验证了MALAT1和miR-9-3p之间的结合关系。有趣的是，突触相关蛋白 97 (SAP97) 是一种众所周知的与突触功能相关的基因，在 VaD 小鼠的海马体中被发现表达上调。对海马神经元进行的体外实验表明，miR-9-3p 负向调节 SAP97 的表达。海马神经元中 MALAT1 的下调增加了 miR-9-3p 并减少了 SAP97，而抑制 miR-9-3p 则挽救了 MALAT1 下调介导的 SAP97 减少。总之，本研究报告了 VaD 小鼠海马中 MALAT1、miR-9-3p 和 SAP97 表达水平的变化，表明 MALAT1 靶向 miR-9-3p 上调 VaD 小鼠海马中 SAP97 。这项工作将有助于理解 VaD 的分子机制。