Czuba-Pakuła Ewelina, Ochocińska Jolanta, Głowiński Sebastian, Braczko Alicja, Smoleński Ryszard T, Lietzau Grażyna, Kowiański Przemysław
Division of Anatomy and Neurobiology, Faculty of Medicine, Medical University of Gdansk, Dębinki 1, 80-211, Gdańsk, Poland.
Department of Conservative Dentistry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
Cell Mol Neurobiol. 2025 May 30;45(1):55. doi: 10.1007/s10571-025-01562-0.
Hypercholesterolemia (Hch) is a risk factor for cerebrovascular and neurodegenerative diseases, manifesting with symptoms that vary depending on damage to specific brain regions. Hch triggers inflammatory responses and cell death. However, the progression of these processes in relation to the duration of Hch and the location of pathology in the central nervous system remains unclear. Therefore, we aimed to investigate (1) the impact of age and duration of Hch on neuroinflammatory responses and programmed cell death in the brain and (2) the intensity of these processes in various brain areas during Hch. In this study, we used 3-, 6-, and 12-month-old male Apo E/LDLR double-knockout mice and age-matched wild-type C57BL/6 mice (control group). Concentrations of cytokines IL-1β, IL-4, and IL-6, as well as apoptotic mediators AIF and Cas-3, were measured using enzyme-linked immunosorbent assay in the whole brain and separately in the prefrontal cortex (PFCx), hippocampus (HIP), and striatum (STR). The results showed that the Hch-induced release of cytokines IL-1β and IL-6, decreased expression of IL-4, and elevated level of apoptotic markers AIF and Cas-3 correlated with Hch duration. The inflammatory response and expression of apoptotic markers were more pronounced in the HIP and STR compared to the PFCx. Our results indicate a correlation between the neurodegenerative effects of Hch and its duration and highlight the varying susceptibility of different brain areas to Hch-induced damage.
高胆固醇血症（Hch）是脑血管疾病和神经退行性疾病的危险因素，其症状因特定脑区受损情况而异。Hch会引发炎症反应和细胞死亡。然而，这些过程与Hch持续时间以及中枢神经系统病理位置的关系仍不清楚。因此，我们旨在研究（1）年龄和Hch持续时间对大脑神经炎症反应和程序性细胞死亡的影响，以及（2）Hch期间不同脑区这些过程的强度。在本研究中，我们使用了3个月、6个月和12个月大的雄性载脂蛋白E/低密度脂蛋白受体双敲除小鼠以及年龄匹配的野生型C57BL/6小鼠（对照组）。使用酶联免疫吸附测定法测量全脑以及前额叶皮质（PFCx）、海马体（HIP）和纹状体（STR）中细胞因子白细胞介素-1β（IL-1β）、白细胞介素-4（IL-4）和白细胞介素-6以及凋亡介质凋亡诱导因子（AIF）和半胱天冬酶-3（Cas-3）的浓度。结果表明，Hch诱导的细胞因子IL-1β和IL-6释放、IL-4表达降低以及凋亡标志物AIF和Cas-3水平升高与Hch持续时间相关。与PFCx相比，HIP和STR中的炎症反应和凋亡标志物表达更为明显。我们的结果表明Hch的神经退行性作用与其持续时间之间存在相关性，并突出了不同脑区对Hch诱导损伤的不同易感性。
