NXP032 ameliorates cognitive impairment by alleviating of neurovascular aging process in aged mice brain

Abstract

Abstract Vascular aging is well known to be associated with breakdown of the neurovascular unit (NVU) that is essential for maintaining brain homeostasis and has been linked to higher cognitive dysfunction. Oxidative stress is believed to be a major cause of the vascular aging process, and damages cerebral parenchymal cells in aged brain. Vitamin C is easily oxidized under human physiologic conditions and loses its potent antioxidant activity. To overcome this limitation, we have developed a DNA aptamer that enhances function of vitamin C; NXP032 is binding form of Aptamer and vitamin C. We investigated microvascular damage, blood-brain barrier (BBB) disruption, glial activation, and cognitive function in 20-month-old mice to confirm the protective effect of NXP032 on vascular aging. NXP032 was treated orally for 8 weeks every day. In this study, we found that aged mice showed obvious cognitive impairment through Y-maze and passive avoidance tests. The microvascular damage was manifested through the decreased length of PECAM-1, lectin. BBB disruption was confirmed through the expression of PDGFR-β, ZO-1 and laminin. Aged mice also showed activation of microglia and astrocytes in the motor cortex and hippocampal CA1 region. These changes were significantly alleviated after the NXP032 treatment in aged mice. Based on the results, we suggest that the NXP032 reduces vascular aging which may be a novel intervention for aging-induced cognitive impairment.