Author:
Lee Jae-Min,Lee Joo Hee,Kim So Hee,Sim Tae Hyeok,Kim Youn-Jung
Abstract
AbstractVascular aging is well known to be associated with the breakdown of the neurovascular unit (NVU), which is essential for maintaining brain homeostasis and linked to higher cognitive dysfunction. Oxidative stress is believed to be a significant cause of the vascular aging process. Vitamin C is easily oxidized under physiological conditions, so it loses its potent antioxidant activity. We developed a DNA aptamer that enhances the function of vitamin C. NXP032 is the binding form of the aptamer and vitamin C. In this study, we investigated the effect of NXP032 on neurovascular stabilization through the changes of PECAM-1, PDGFR-β, ZO-1, laminin, and glial cells involved in maintaining the integrity of the blood–brain barrier (BBB) in aged mice. NXP032 was orally administered daily for 8 weeks. Compared to young mice and NXP032-treated mice, 20-month-old mice displayed cognitive impairments in Y-maze and passive avoidance tests. NXP032 treatment contributed to reducing the BBB damage by attenuating the fragmentation of microvessels and reducing PDGFR-β, ZO-1, and laminin expression, thereby mitigating astrocytes and microglia activation during normal aging. Based on the results, we suggest that NXP032 reduces vascular aging and may be a novel intervention for aging-induced cognitive impairment.
Funder
Nexmos
National Research Foundation of Korea
Publisher
Springer Science and Business Media LLC
Reference48 articles.
1. Rinaldi, C. et al. Oxidative stress and the neurovascular unit. Life 11, 767. https://doi.org/10.3390/life11080767 (2021).
2. Chen, L. & Liu, B. Relationships between stress granules, oxidative stress, and neurodegenerative diseases. Oxid. Med. Cell Longev. 2017, 1–10 (2017).
3. Keaney, J. & Campbell, M. The dynamic blood-brain barrier. FEBS J. 282, 4067–4079. https://doi.org/10.1111/febs.13412 (2015).
4. Erdő, F., Denes, L. & de Lange, E. Age-associated physiological and pathological changes at the blood-brain barrier: A review. J. Cereb. Blood Flow. Metab. 37, 4–24. https://doi.org/10.1177/0271678X16679420 (2017).
5. Varatharaj, A. & Galea, I. The blood-brain barrier in systemic inflammation. Brain Behav. Immun. 60, 1–12. https://doi.org/10.1016/j.bbi.2016.03.010 (2017).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献