Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan.
Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan.
Lipids Health Dis. 2024 Aug 17;23(1):250. doi: 10.1186/s12944-024-02236-4.
Hypercholesterolemia is associated with increased inflammation and impaired serotonin neurotransmission, potentially contributing to depressive symptoms. However, the role of statins, particularly pitavastatin, in modulating serotonin transporter (SERT) function within this context remains underexplored. This study aimed to investigate whether pitavastatin counteracts the neurobiological effects of hypercholesterolemia.
Low-density lipoprotein receptor knockout (LDLR) mice on a C57BL/6 background were assigned to three groups: a control group fed a standard chow diet, a group fed a high-fat diet (HFD), and a third group fed a high-fat diet supplemented with pitavastatin (HFD + Pita). We evaluated the effects of HFD with or without pitavastatin on lipid profiles, inflammatory markers, and SERT availability using small-animal positron emission tomography (PET) scans with the radioligand 4-[F]-ADAM over a 20-week period.
Pitavastatin treatment in HFD-fed mice significantly reduced both total cholesterol and LDL cholesterol levels in HFD-fed mice compared to those on HFD alone. Elevated inflammatory markers such as IL-1α, MCP-1/CCL2, and TNF-α in HFD mice were notably decreased in the HFD + Pita group. PET scans showed reduced SERT availability in the brains of HFD mice; however, pitavastatin improved this in brain regions associated with mood regulation, suggesting enhanced serotonin neurotransmission. Additionally, the sucrose preference test showed a trend towards increased preference in the HFD + Pita group compared to the HFD group, indicating a potential reduction in depressive-like behavior.
Our findings demonstrate that pitavastatin not only lowers cholesterol and reduces inflammation but also enhances SERT availability, suggesting a potential role in alleviating depressive symptoms associated with hypercholesterolemia. These results highlight the multifaceted benefits of pitavastatin, extending beyond its lipid-lowering effects to potentially improving mood regulation and neurotransmitter function.
高胆固醇血症与炎症增加和 5-羟色胺神经递质传递受损有关，可能导致抑郁症状。然而，他汀类药物，特别是匹伐他汀，在调节这种情况下的 5-羟色胺转运体（SERT）功能方面的作用仍未得到充分探索。本研究旨在探讨匹伐他汀是否能对抗高胆固醇血症的神经生物学效应。
低密度脂蛋白受体敲除（LDLR）小鼠在 C57BL/6 背景下分为三组：一组给予标准饲料，一组给予高脂肪饮食（HFD），第三组给予高脂肪饮食加匹伐他汀（HFD+Pita）。我们使用 4-[F]-ADAM 放射性配体通过小动物正电子发射断层扫描（PET）在 20 周的时间内评估 HFD 加或不加匹伐他汀对血脂谱、炎症标志物和 SERT 可及性的影响。
与单独给予 HFD 的小鼠相比，匹伐他汀治疗可显著降低 HFD 喂养小鼠的总胆固醇和 LDL 胆固醇水平。HFD 小鼠中升高的炎症标志物，如 IL-1α、MCP-1/CCL2 和 TNF-α，在 HFD+Pita 组中明显降低。PET 扫描显示 HFD 小鼠大脑中的 SERT 可及性降低；然而，匹伐他汀改善了与情绪调节相关的大脑区域的这种情况，提示增强了 5-羟色胺神经递质传递。此外，蔗糖偏好试验显示 HFD+Pita 组与 HFD 组相比，对蔗糖的偏好呈增加趋势，表明潜在的抑郁样行为减少。
我们的研究结果表明，匹伐他汀不仅降低胆固醇和减少炎症，而且增强 SERT 可及性，表明其在缓解与高胆固醇血症相关的抑郁症状方面具有潜在作用。这些结果强调了匹伐他汀的多方面益处，不仅限于其降脂作用，还可能改善情绪调节和神经递质功能。
