BACKGROUND The circumventricular organs (CVOs) are blood-brain-barrier missing structures whose activation through lipopolysaccharide (LPS) is a starting point for TLR-driven (Toll-like receptors) neuroinflammation. The aim of this study was to evaluate in the CVO area postrema (AP), subfornical organ (SFO), and median eminence (ME), the inflammatory response to two TLR4 agonists: LPS from Escherichia coli (EC-LPS), the strongest endotoxin molecule described, and LPS from Porphyromonas gingivalis (PG-LPS), a pathogenic bacteria present in the periodontium related to neuroinflammation in neurodegenerative/psychiatric diseases. The response to LPS from the cyanobacteria Rhodobacter sphaeroides (RS-LPS), a TLR4 antagonist with an interesting anti-inflammatory potential, was also assessed. METHODS LPSs were intraperitoneally administered to Wistar rats and, as indicatives of neuroinflammation in CVOs, the cellular localization of the nuclear factor NF-κB was studied by immunofluorescence, and microglia morphology was quantified by fractal and skeleton analysis. RESULTS Data showed that EC-LPS increased NF-κB nuclear translocation in the three CVOs studied and PG-LPS only induced NF-κB nuclear translocation in the ME. RS-LPS showed no difference in NF-κB nuclear translocation compared to control. Microglia in the three CVOs showed an ameboid-shape after EC-LPS exposure, whereas PG-LPS only elicited a mild tendency to induce an ameboid shape. On the other hand, RS-LPS produced a markedly elongated morphology described as "rod" microglia in the three CVOs. CONCLUSIONS In conclusion, at the doses tested, EC-LPS induces a stronger neuroinflammatory response than PG-LPS in CVOs, which might be related to their different potency as TLR4 agonists. The non-reduction of basal NF-κB activation and induction of rod microglia by RS-LPS, a cell morphology only present in severe brain injury and infections, suggests that this molecule must be carefully studied before being proposed as an anti-inflammatory treatment for neuroinflammation related to neurodegenerative/psychiatric diseases.

中文翻译：

---

Toll样受体4激动剂和拮抗剂脂多糖可改变大鼠脑室室管器官的先天免疫应答。

背景技术室脑器官（CVO）是血脑屏障缺失的结构，其通过脂多糖（LPS）的激活是TLR驱动的（Toll样受体）神经炎症的起点。这项研究的目的是评估CVO区的后部（AP），分支下器官（SFO）和中位隆起（ME）对两种TLR4激动剂的炎症反应：最强的大肠杆菌LPS（EC-LPS）。描述的内毒素分子和牙龈卟啉单胞菌（PG-LPS）的LPS，牙周炎中的一种致病细菌与神经退行性/精神疾病中的神经炎症有关。还评估了来自蓝细菌球形球形红细菌（RS-LPS）对LPS的反应，该细菌是一种具有令人感兴趣的抗炎潜力的TLR4拮抗剂。方法对Wistar大鼠腹膜内给予LPS，并通过免疫荧光研究核因子NF-κB的细胞定位，并通过分形和骨架分析对小胶质细胞形态进行定量分析，以作为CVO中神经炎症的指标。结果数据显示，EC-LPS增加了所研究的三个CVO中的NF-κB核易位，而PG-LPS仅诱导了ME中的NF-κB核易位。与对照组相比，RS-LPS的NF-κB核移位没有差异。在暴露于EC-LPS后，三个CVO中的小胶质细胞显示出类eb形，而PG-LPS仅引起轻度的诱导类tendency形的趋势。另一方面，RS-LPS在三个CVO中产生了明显伸长的形态，称为“杆状”小胶质细胞。结论总而言之，在所测试的剂量下，EC-LPS在CVO中比PG-LPS诱导更强的神经炎症反应，这可能与其作为TLR4激动剂的功效不同有关。RS-LPS（仅在严重的脑损伤和感染中才存在的一种细胞形态）不降低基础NF-κB的活化并诱导杆状小胶质细胞，这表明该分子在被提议用作抗炎治疗前必须进行仔细研究。与神经退行性/精神疾病有关的神经炎症。