Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Behav Brain Res. 2023 Sep 13;453:114611. doi: 10.1016/j.bbr.2023.114611. Epub 2023 Aug 3.
Alzheimer's disease (AD) is the most prevalent form of dementia with multiple etiology and no effective remedy. Statins are a group of medicines that are basically used to lower cholesterol. However, several studies have recently done to assess the potential relationship between statins use and dementia but presented controversial results.
In this study, using ovariectomy and D-galactose injection, a model of AD was induced in female rats, and then the protective effects of oral administration of simvastatin were investigated. shuttle box and Y-maze tests were done to assess the animals' learning and memory performance. Using GC-MC, ELISA, Immunohistochemistry and tissue staining techniques, changes in the amount of short-chain fatty acids (SCFAs), plasma and hippocampus neuroinflammatory markers and histological changes in the intestine and hippocampus were assessed in sham, disease and treatment groups.
Oral administration of simvastatin improved the gut microbiome activity (increased the amount of SCFAs in fecal samples) and strengthened the tight junctions of intestinal cells. Moreover, simvastatin reduced the amount of TNF-α and IL-1β in plasma and hippocampus. Also, cell death and Amyloid plaques notably decreased in the simvastatin-treated hippocampal tissue. All these physiological changes led to better performance in behavioral tasks in the treatment group in comparison to the disease group.
These findings provide evidence that simvastatin may improve gut-brain axis followed by improvement in learning and memory via an anti-inflammatory effect.
阿尔茨海默病（AD）是最常见的痴呆症形式，病因多样，尚无有效治疗方法。他汀类药物是一组基本用于降低胆固醇的药物。然而，最近有几项研究评估了他汀类药物使用与痴呆症之间的潜在关系，但结果存在争议。
在这项研究中，通过卵巢切除术和 D-半乳糖注射，诱导雌性大鼠 AD 模型，然后研究辛伐他汀口服给药的保护作用。穿梭箱和 Y 迷宫测试用于评估动物的学习和记忆表现。使用 GC-MC、ELISA、免疫组织化学和组织染色技术，评估假手术、疾病和治疗组中短链脂肪酸 (SCFA) 量、血浆和海马神经炎症标志物以及肠道和海马组织的组织学变化。
辛伐他汀的口服给药改善了肠道微生物组的活性（粪便样本中 SCFA 的量增加），并增强了肠道细胞的紧密连接。此外，辛伐他汀降低了血浆和海马中的 TNF-α 和 IL-1β 含量。此外，辛伐他汀治疗的海马组织中的细胞死亡和淀粉样斑块明显减少。所有这些生理变化导致治疗组在行为任务中的表现优于疾病组。
这些发现提供了证据表明，辛伐他汀可能通过抗炎作用改善肠脑轴，从而改善学习和记忆。
