Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Department of Pharmacology and Toxicology (Graduate Student), Pharmacy College, King Saud University, Riyadh 11495, Saudi Arabia.
Int J Mol Sci. 2024 Jul 16;25(14):7768. doi: 10.3390/ijms25147768.
Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice ( mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in control mice than in all remaining groups. Identifying the factors that increase the BBB in mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.
2 型糖尿病(T2DM)与多种并发症相关,包括认知障碍,且 T2DM 患者中与记忆相关的神经退行性疾病的患病率更高。一种可能的理论是血脑屏障(BBB)的微血管和大血管环境发生改变。在这项研究中,我们采用了包括 RT-PCR 在内的不同方法、利用荧光素钠(NaFL)进行功能性药代动力学研究以及共聚焦显微镜检查,以表征 T2DM 动物模型(瘦素受体缺陷型突变小鼠)中 BBB 的功能和分子完整性。结果显示,与同窝野生型小鼠相比,该动物模型中 VCAM-1、ICAM-1、MMP-9 和 S100b(BBB 相关标志物)出现失调。未经处理的 小鼠脑中的荧光素钠(NaFL)浓度明显高于经胰岛素处理的小鼠。因此,与其余所有组相比,NaFL 在对照小鼠中的通透性更高。鉴定出增加 小鼠 BBB 的因素将有助于更好地了解 BBB 的微血管,并呈现出以前未描述的与 T2DM 相关的脑部疾病发现,填补这一新兴研究领域的知识空白。