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 (BCSFB), 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 (CSF) and hippocampal tissue. Interestingly, LYCO administration, HAECs transplantation and their combination reversed the Aβ_1–42 induced up-regulation of Toll like receptor 4 (TLR4) and nuclear factor- κB p65 (NF-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.

以神经胶质激活和促炎介质释放为特征的神经炎症被认为与阿尔茨海默病 (AD) 的认知缺陷有关。此前，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 的炎症。具体而言，脉络丛 (CP) 是一种形成血脑脊液屏障 (BCSFB) 的上皮层，能够通过神经炎症反应和脑免疫监视的变化来调节认知功能。然而，尚不清楚 LYCO 是否可以与 HAEC 相互作用以改善 CP 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 HAEC 组合的可行性，作为急性诱导 AD 大鼠模型中 CP 免疫调节作用的治疗剂。结果表明，口服LYCO、HAECs移植及其组合可显着改善水迷宫试验中的认知缺陷，降低促炎介质（TNF-α和IL-1β）水平，增加抗炎介质（IL-10）水平。和 TGF-β1) 在脑脊液 (CSF) 和海马组织中。有趣的是，LYCO 给药、HAECs 移植及其组合逆转了 Aβ 增加脑脊液 (CSF) 和海马组织中抗炎介质 (IL-10 和 TGF-β1) 的水平。有趣的是，LYCO 给药、HAECs 移植及其组合逆转了 Aβ 增加脑脊液 (CSF) 和海马组织中抗炎介质 (IL-10 和 TGF-β1) 的水平。有趣的是，LYCO 给药、HAECs 移植及其组合逆转了 Aβ_1-42在 CP 诱导 Toll 样受体 4 (TLR4) 和核因子-κB p65 (NF-κB p65) mRNA 和蛋白质表达的上调。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。它还可能为 AD 的病理生理学和 CP 的相关潜在机制提供治疗窗口。