Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia.
Interoception Laboratory, Pavlov Institute of Physiology RAS, 199034 St. Petersburg, Russia.
Int J Mol Sci. 2023 Dec 24;25(1):276. doi: 10.3390/ijms25010276.
Endothelial cells in brain capillaries are crucial for the function of the blood-brain barrier (BBB), and members of the tight junction protein family of claudins are regarded to be primarily responsible for barrier properties. Thus, the analysis of bioactive substances that can affect the BBB's permeability is of great importance and may be useful for the development of new therapeutic strategies for brain pathologies. In our study, we tested the hypothesis that the application of the glucocorticoid prednisolone affects the murine blood-brain barrier in vivo. Isolated brain tissue of control and prednisolone-injected mice was examined by employing immunoblotting and confocal laser scanning immunofluorescence microscopy, and the physiological and behavioral effects were analyzed. The control tissue samples revealed the expression of barrier-forming tight junction proteins claudin-1, -3, and -5 and of the paracellular cation and water-channel-forming protein claudin-2. Prednisolone administration for 7 days at doses of 70 mg/kg caused physiological and behavioral effects and downregulated claudin-1 and -3 and the channel-forming claudin-2 without altering their localization in cerebral blood vessels. Changes in the expression of these claudins might have effects on the ionic and acid-base balance in brain tissue, suggesting the relevance of our findings for therapeutic options in disorders such as cerebral edema and psychiatric failure.
脑毛细血管内皮细胞对于血脑屏障（BBB）的功能至关重要，而紧密连接蛋白家族成员 Claudin 被认为主要负责屏障特性。因此，分析能够影响 BBB 通透性的生物活性物质具有重要意义，可能有助于开发治疗脑病理学的新治疗策略。在我们的研究中，我们检验了应用糖皮质激素泼尼松龙是否会影响体内小鼠血脑屏障的假说。通过免疫印迹和共聚焦激光扫描免疫荧光显微镜检查，对对照和泼尼松龙注射小鼠的离体脑组织进行了检查，并分析了生理和行为效应。对照组织样本显示出形成屏障的紧密连接蛋白 Claudin-1、-3 和 -5 以及细胞旁阳离子和水通道形成蛋白 Claudin-2 的表达。在 70mg/kg 的剂量下，泼尼松龙连续给药 7 天会引起生理和行为效应，并下调 Claudin-1 和 -3 以及形成通道的 Claudin-2，而不会改变它们在脑血管中的定位。这些 Claudin 的表达变化可能会对脑组织中的离子和酸碱平衡产生影响，这表明我们的发现对于脑水肿和精神衰竭等疾病的治疗选择具有相关性。
