Bacteria-associated VB12 regulates neonatal ileal epithelium homeostasis

项目总结/摘要 阿尔茨海默病和相关痴呆（ADRD）严重削弱宿主记忆和宿主功能， 能力因此，目前没有有效的治疗策略可用于转化为临床环境。 研究阐明了微量营养素的关键作用（例如，维生素、氨基酸）， 神经退行性变，导致宿主认知能力下降。因此，阐明微量营养素- 依赖方法可以减轻主机存储器损失。维生素B12（VB 12）是维持身体健康的关键因素。 肠上皮平衡和功能性微生物组生理学对抗诱导的毒性炎症。 相比之下，VB 12缺乏会使致病性炎症持续存在，最终导致肠道组织的破坏。 分子稳态此外，我们还发现，VB 12在功能上调节TGFs、小胶质细胞和大脑皮层。 脂质体，所有这些都可以控制诱导的神经炎症。为了进一步深入研究VB 12在功能上的能力， 维持大脑紧张状态，以潜在地控制tau蛋白病病理，本行政管理的目的是 补充研究建议是进一步阐明VB 12参与大脑功能的硬连线， 限制小胶质细胞的不受控制的激活，可能涉及tau蛋白病依赖性记忆衰退。 我们的假设是，VB 12紧密地维持大脑Treg稳态，以限制tau蛋白病相关的脑损伤。 神经炎症，导致宿主记忆丧失的显著改善。具体目标是：1. 研究VB 12在维持功能性脑神经张力以限制tau蛋白病病理学中的相关性，以及2. 阐明TGFAP对小胶质细胞的调节，可能有助于改善记忆 下降这一行政补充研究提案的预测结果将是第一次深入 报告了VB 12通过功能性TdR紧张性调节脑内稳态以潜在地减少宿主 记忆衰退

Project Summary/Abstract Alzheimer's disease and related dementias (ADRD) critically debilitate the host memory, and host functional ability. Accordingly, no efficacious therapeutic strategies are currently available to translate into clinical settings. Studies illuminate the pivotal role of micronutrients (e.g., vitamins, amino acids) in alleviating induced neurodegeneration, resulting in the improvement of host cognitive decline. Thus, elucidating micronutrient- dependent approaches may mitigate host memory loss. Vitamin B12 (VB12) is a crucial factor that sustains the intestinal epithelium equilibrium, and functional microbiome physiology against induced toxic inflammation. Contrastingly, VB12-deficiency perpetuates pathogenic inflammation, culminating in the disruption of intestinal molecular homeostasis. Additionally, we show that VB12 functionally regulates Tregs, microglia, and the cerebral lipidomes, all of which may control induced neuroinflammation. To further delve into VB12’s ability in functionally sustaining cerebral Tregs to potentially control tauopathy pathology, the objective of this administrative supplement research proposal is to further elucidate VB12-involvement in hardwiring the functions of cerebral Tregs to limit uncontrolled activation of microglia, potentially implicated in tauopathy-dependent memory decline. Our hypothesis is that VB12 tightly maintains the cerebral Treg homeostasis to limit tauopathy-associated neuroinflammation, leading to significant improvement of the host memory loss. The specific aims are: 1. Investigate the relevance of VB12 in maintaining functional cerebral Tregs to limit tauopathy pathology, and 2. Elucidate the regulation of microglia cells by Tregs, potentially contributing to the improvement of memory decline. The predicted outcomes of this administrative supplement research proposal will be the first in-depth report on VB12 in tonically regulating brain homeostasis through functional Tregs to potentially reduce host memory decline.