NXP032 ameliorates cognitive impairment by alleviating the neurovascular aging process in aged mouse brain

Abstract

Abstract Vascular 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.