Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Center of Excellence for Aging and Brain Repair, USFHealth, Tampa, Florida 33612, USA.
Rejuvenation Res. 2010 Oct;13(5):581-8. doi: 10.1089/rej.2009.1011. Epub 2010 Jun 29.
The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche.
衰老是与氧化应激、小胶质细胞激活和促炎因子相关联的，这些因子已知会降低细胞增殖并限制神经可塑性。这些因子可能导致正常衰老向更严重的与神经退行性疾病相关的认知功能障碍的转变。我们已经表明，蓝莓和绿茶中的多酚等天然化合物以及肌肽等氨基酸具有很高的抗氧化和抗炎活性，可以减少血液、大脑和身体其他组织中活性氧 (ROS) 的破坏性影响。此外，我们已经表明，这些营养素（称为 NT-020）的组合产生协同作用，促进体外和体内干细胞的增殖。在当前的研究中，我们研究了 NT-020 对神经发生和 Morris 水迷宫 (MWM) 表现的影响。用 135.0mg/kg/天（n=13）的 NT-020 处理 20 月龄雄性 Fischer 344 大鼠（n=13）。用口服灌胃法处理 3 月龄（n=10）和 20 月龄（n=13）的年轻和老年雄性 Fischer 344 大鼠。所有组均治疗 4 周。虽然比较所有老年大鼠的 MWM 表现时没有差异，但当比较老年受损大鼠的数据时，治疗组在训练的最后一天与对照组之间存在显著差异，治疗组的表现优于对照组。使用细胞周期调节蛋白（Ki67）、双皮质素（DCX）和 OX6 抗体标志物，估计年轻和老年动物齿状回（DG）中的细胞增殖、神经发生和小胶质细胞激活。还检查了 SVZ 中的细胞增殖。与老年对照组相比，用 NT-020 处理的大鼠中发现 OX6 MHC II 阳性细胞数量减少、神经发生增加和增殖细胞数量增加。总之，NT-020 可能会促进老年动物的健康、增殖和神经元维持，并发挥抗炎作用，促进老年干细胞龛中的功能。
