Flowers Antwoine, Lee Jea-Young, Acosta Sandra, Hudson Charles, Small Brent, Sanberg Cyndy D, Bickford Paula C
Department of Neurosurgery Brain Repair, and Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, MDC-78, 12901 Bruce B Downs, Blvd, Tampa, FL, 33612, USA.
Research Service, James A Haley Veterans Hospital, Tampa, FL, USA.
J Neuroinflammation. 2015 Sep 17;12:174. doi: 10.1186/s12974-015-0395-4.
Aging is associated with a decline in stem cell proliferation that is thought to be a result of dysregulated signaling in the neurogenic niche. This results in a diminished and less efficient pool of progenitors. The Wnt pathway plays a key role in the proliferation and differentiation of progenitor cells. Recent publications suggest that the age-related decline in the function of Wnt is a contributor to age-dependent decline in neural progenitors. Similarly, the aged neurogenic niche is characterized by higher levels of inflammatory cytokines. This increased inflammation contributes to the declining function of neural progenitor cells. NT-020, a proprietary blend of polyphenols, has been shown to increase proliferation of neural progenitors and improve cognitive function in aged rats.
In this study, we examined the neurogenic niche in the subgranular zone of the dentate gyrus (SGZ) and the subventricular zone (SVZ) of young and aged rats to determine if dietary supplementation with NT-020 could regulate inflammation and oxidative stress response pathways in neurons, astrocytes, and microglia. Further, we examined NT-020's ability to modulate Wnt signaling in the aged neurogenic niche. To accomplish this, we utilized gene PCR arrays and immunohistochemistry.
We observed an increase in nuclear localization of immunopositive labeling of β-catenin, HO-1, and Nrf2 in all subsets of cell types in both young and aged rats in the SGZ and SVZ following NT-020 treatment. NeuN-positive cells showed a basal increase in nuclear β-catenin in the aged rats, which was not observed in doublecortin (DCX)-labeled cells, microglia, or astrocytes. Reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated hippocampal tissue revealed that a significant percent of genes involved with inflammation are affected by treatment with NT-020. In addition, several genes that regulate Wnt activity were affected by supplementation.
The results suggest that NT-020 activates oxidative stress response pathways and supports pro-neurogenic gene expression in the hippocampus. This may represent the mechanism by which the NT-020 formula enhances performance in learning and memory tasks in aged mice.
衰老与干细胞增殖能力下降有关，这被认为是神经源性微环境中信号失调的结果。这导致祖细胞池减少且效率降低。Wnt信号通路在祖细胞的增殖和分化中起关键作用。最近的出版物表明，与年龄相关的Wnt功能下降是神经祖细胞随年龄下降的一个因素。同样，衰老的神经源性微环境的特征是炎症细胞因子水平较高。这种炎症增加导致神经祖细胞功能下降。NT - 020是一种多酚的专利混合物，已被证明能增加老年大鼠神经祖细胞的增殖并改善其认知功能。
在本研究中，我们检查了年轻和老年大鼠齿状回颗粒下区（SGZ）和脑室下区（SVZ）的神经源性微环境，以确定补充NT - 020饮食是否能调节神经元、星形胶质细胞和小胶质细胞中的炎症和氧化应激反应途径。此外，我们研究了NT - 020调节衰老神经源性微环境中Wnt信号的能力。为此，我们使用了基因PCR阵列和免疫组织化学方法。
我们观察到，在NT - 020处理后，年轻和老年大鼠SGZ和SVZ中所有细胞类型亚群中，β-连环蛋白、HO - 1和Nrf2免疫阳性标记的核定位增加。在老年大鼠中，NeuN阳性细胞的核β-连环蛋白有基础增加，而在双皮质素（DCX）标记的细胞、小胶质细胞或星形胶质细胞中未观察到这种情况。对分离的海马组织进行逆转录聚合酶链反应（RT - PCR）分析显示，相当一部分与炎症相关的基因受到NT - 020处理的影响。此外，一些调节Wnt活性的基因也受到补充剂的影响。
结果表明，NT - 020激活氧化应激反应途径并支持海马体中促神经源性基因的表达。这可能代表了NT - 020配方增强老年小鼠学习和记忆任务表现的机制。
