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.
Purpose: This study was conducted to assess the antidepressant effects of capsaicin in chronic depressive rats and elucidate the mechanism underlying its effects.Methods: Male Wistar rats (280~320 g, 8 weeks of age) were subjected to depression induced by chronic unpredictable mild stresses. The rats were exposed to 8 kinds of stresses for 8 weeks. In the last 2 weeks, fluoxetine or capsaicin was injected subcutaneously. The dose of fluoxetine was 10 mg/kg (body weight), while the doses of capsaicin consisted of low (1 mg/kg), middle (5 mg/kg), and high (10 mg/kg). The forced swim test (FST) was conducted to evaluate the immobility time of rats. The immobility time indicates despair, one of symptoms of depression. The change of tryptophan hydroxylase (TPH) in the dorsal raphe was investigated using immunohistochemistry. In the hippocampus cornu ammonis (CA) 1 and 3, glucocorticoid receptor (GR) expression was measured.Results: The immobility time in the FST was significantly lower (p < .05) in the low-dose (M = 32.40 ± 13.41 seconds) and middle-dose (M = 28.48 ± 19.57 seconds) groups than in the non-treated depressive rats (M = 90.19 ± 45.34 seconds). The amount of TPH in the dorsal raphe was significantly higher (p < .05) in the middle-dose (M = 249.17 ± 35.02) and high-dose (M = 251.0 ± 56.85) groups than in the non-treated depressive rats (M = 159.78 ± 41.16). However, GR expression in the hippocampus CA1 and CA3 did not show significant differences between the non-treated depressive rats and the capsaicin-injected rats.Conclusion: This study suggests that capsaicin produces an antidepressant-like effect on chronic unpredictable mild stress-induced depression in rats via the serotonin biosynthesis pathway.
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.
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