Xiehe Union East China Stem Cell & Gene Engineering Corp., Ltd; Zhejiang Umbilical Cord Blood Hematopoietic Stem Cell Bank; Huzhou, Zhejiang Province, P. R. China.
Department of Physiology, Huzhou University, Huzhou, Zhejiang Province, P. R. China.
J Nutr Biochem. 2021 Feb;88:108558. doi: 10.1016/j.jnutbio.2020.108558. Epub 2020 Nov 26.
Neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to be correlated with cognitive deficits in Alzheimer's disease (AD). Previously, some studies have demonstrated that lycopene (LYCO) or human amniotic epithelial cells (HAECs) could attenuate inflammation in AD. Specifically, the choroid plexus (CP), an epithelial layer that forms the blood-cerebrospinal fluid barrier, is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, it is unclear if LYCO can interact with HAECs to improve neuroinflammation at the CP. Thus, this study chose the region of interest, considered the feasibility of using a combination of LYCO and HAECs, as a therapeutic agent for immunomodulatory effects at the CP in an acutely induced AD rat model. Results showed that oral administration of LYCO, HAECs transplantation, and their combination significantly improved cognitive deficits in water maze test, decreased the level of proinflammatory mediators (TNF-α and IL-1β), increased the level of anti-inflammatory mediators (IL-10 and TGF-β1) in the cerebro-spinal fluid, and hippocampal tissue. Interestingly, LYCO administration, HAECs transplantation and their combination reversed the Aβ induced up-regulation of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein expressions at the CP. This study provided the novel experimental evidence for the influence of co-treatment with LYCO and HAECs on immunomodulatory capabilities of CP. It could also warrant therapeutic window for the pathophysiology of AD and the associated underlying mechanisms at the CP.
神经炎症表现为神经胶质细胞的激活和促炎介质的释放,被认为与阿尔茨海默病(AD)的认知缺陷有关。以前的一些研究表明,番茄红素(LYCO)或人羊膜上皮细胞(HAECs)可以减轻 AD 中的炎症。具体来说,脉络丛(CP)是形成血脑屏障的上皮层,能够通过改变神经炎症反应和大脑免疫监视来调节认知功能。然而,目前尚不清楚 LYCO 是否可以与 HAECs 相互作用,以改善 CP 中的神经炎症。因此,本研究选择了感兴趣的区域,考虑了使用 LYCO 和 HAECs 联合作为治疗剂在急性诱导的 AD 大鼠模型中对 CP 进行免疫调节作用的可行性。结果表明,LYCO 口服给药、HAECs 移植及其组合显著改善了水迷宫测试中的认知缺陷,降低了脑脊液中促炎介质(TNF-α和 IL-1β)的水平,增加了抗炎介质(IL-10 和 TGF-β1)的水平在海马组织中。有趣的是,LYCO 给药、HAECs 移植及其组合逆转了 Aβ 诱导的 CP 中 Toll 样受体 4 和核因子-κB p65 mRNA 和蛋白表达的上调。本研究为 LYCO 和 HAECs 联合治疗对 CP 免疫调节能力的影响提供了新的实验证据。它还可以为 AD 的病理生理学和 CP 相关的潜在机制提供治疗窗口。