Pham Viana Q, Tutunculer Melike, Al-Dulaimi Halah, Ardjmand Daniel, Fleischmann William, Bachor Tomas P, Xu Allison W
Diabetes Center and Department of Anatomy, University of California, San Francisco, San Francisco, CA, United States.
Front Aging Neurosci. 2025 Aug 19;17:1634283. doi: 10.3389/fnagi.2025.1634283. eCollection 2025.
Effective communication between the brain and peripheral tissues is crucial for homeostasis and health, and its impairment is a defining feature of aging. Circumventricular organs, characterized by the presence of fenestrated capillaries and absence of a blood-brain barrier (BBB), play a crucial role in controlling substance exchange between the brain and the blood. To date, adaptive changes in fenestrated vasculature in response to environmental insults remain poorly understood. In this study, we show that fenestrated capillaries in the median eminence (ME) and area postrema (AP)-two distinct circumventricular organs critical for metabolic control-undergo differential remodeling when exposed to circulating monosodium glutamate (MSG), a BBB-impermeable neurotoxin. Upon MSG exposure, fenestrated capillaries and vascular permeability were decreased in the ME but increased in the AP, and these changes were closely associated with the expression of angiogenic factors pleiotrophin () and vascular endothelial growth factor A (). In both ME and AP, adult tanycytes expressed high levels of and have processes in close contact with fenestrated capillaries. Significantly, the adaptive regulation of expression and the ability to modulate fenestrated capillaries and vascular permeability were abolished in both ME and AP of aged animals. Together, our findings suggest that tanycytic expressions of the angiogenic factor PTN, in conjunction with VEGF, are differentially regulated in distinct circumventricular organs upon exposure to neurotoxins, leading to region-specific remodeling of fenestrated endothelium. Our study further demonstrates that the loss of plasticity in fenestrated vasculature may be a hallmark feature of brain aging.
大脑与外周组织之间的有效沟通对于体内平衡和健康至关重要，而其功能受损是衰老的一个显著特征。室周器官的特点是存在有孔毛细血管且没有血脑屏障（BBB），在控制大脑与血液之间的物质交换中起着关键作用。迄今为止，有孔血管系统对环境损伤的适应性变化仍知之甚少。在本研究中，我们发现，正中隆起（ME）和最后区（AP）这两个对代谢控制至关重要的不同室周器官中的有孔毛细血管，在暴露于循环中的味精（MSG，一种不能透过血脑屏障的神经毒素）时会发生不同的重塑。暴露于味精后，ME中的有孔毛细血管和血管通透性降低，而AP中的则增加，这些变化与血管生成因子多效蛋白（PTN）和血管内皮生长因子A（VEGF）的表达密切相关。在ME和AP中，成年室管膜细胞均高表达PTN且其突起与有孔毛细血管紧密接触。值得注意的是，老年动物的ME和AP中，PTN表达的适应性调节以及调节有孔毛细血管和血管通透性的能力均被消除。总之，我们的研究结果表明，暴露于神经毒素后，血管生成因子PTN与VEGF在不同室周器官中的室管膜细胞表达受到差异调节，导致有孔内皮细胞发生区域特异性重塑。我们的研究进一步证明，有孔血管系统可塑性的丧失可能是大脑衰老的一个标志性特征。
