中文摘要：
Ⅱ型干扰素（IFN‑γ）是一种促炎型T淋巴细胞细胞因子。在病理条件下复杂的小胶质细胞活化过程中，它可对中枢神经系统驻留巨噬细胞 —— 小胶质细胞发挥预激活作用。预激活通常会使小胶质细胞在受到二次炎症刺激时产生放大的应答反应。然而，预激活后的小胶质细胞对于完整皮层组织（原位）内神经元生理功能的影响尚不明确。本研究利用海马脑片培养模型（即出生后脑实质组织，无白细胞浸润、不涉及适应性免疫），探究长期IFN‑γ 暴露对小胶质细胞的作用。研究重点关注γ频段（30‑70 Hz）快速神经元网络振荡。γ振荡是感知、注意力、记忆等高级脑功能的基础，并且对代谢应激与氧化应激高度敏感。
IFN‑γ可诱导小胶质细胞发生显著的形态学改变、细胞数量增多，同时适度上调活化标志物（MHC‑Ⅱ、CD86、IL‑6 与诱导型一氧化氮合酶 iNOS），但并不会上调TNF‑α。锥体神经元与小白蛋白阳性抑制性中间神经元的细胞构筑及形态均保持完好。值得注意的是，γ振荡出现特异性频率下降，降幅最高可达8 Hz；而IFN‑α 或IL‑17 处理并不会复制该效应。通过小胶质细胞药物耗竭实验与iNOS抑制实验证实，该节律紊乱由小胶质细胞适度释放一氧化氮（NO）所介导。
综上，IFN‑γ预激活能够诱导小胶质细胞明显增殖与中度活化，进而减慢神经信息处理速度。在以IFN‑γ水平升高、血脑屏障渗漏和/或T细胞浸润为特征的慢性脑部疾病中，该机制可能在神经退行性病变发生之前，就已经参与认知功能损伤。
英文摘要：
Type II IFN (IFN-γ) is a proinflammatory T lymphocyte cytokine that serves in priming of microglia—resident CNS macrophages—during the complex microglial activation process under pathological conditions. Priming generally permits an exaggerated microglial response to a secondary inflammatory stimulus. The impact of primed microglia on physiological neuronal function in intact cortical tissue (in situ) is widely unknown, however. We explored the effects of chronic IFN-γ exposure on microglia in hippocampal slice cultures, i.e., postnatal parenchyma lacking leukocyte infiltration (adaptive immunity). We focused on fast neuronal network waves in the gamma-band (30–70 Hz). Such gamma oscillations are fundamental to higher brain functions, such as perception, attention, and memory, and are exquisitely sensitive to metabolic and oxidative stress. IFN-γ induced substantial morphological changes and cell population expansion in microglia as well as moderate up-regulation of activation markers, MHC-II, CD86, IL-6, and inducible nitric oxide synthase (iNOS), but not TNF-α. Cytoarchitecture and morphology of pyramidal neurons and parvalbumin-positive inhibitory interneurons were well-preserved. Notably, gamma oscillations showed a specific decline in frequency of up to 8 Hz, which was not mimicked by IFN-α or IL-17 exposure. The rhythm disturbance was caused by moderate microglial nitric oxide (NO) release demonstrated by pharmacological microglia depletion and iNOS inhibition. In conclusion, IFN-γ priming induces substantial proliferation and moderate activation of microglia that is capable of slowing neural information processing. This mechanism might contribute to cognitive impairment in chronic brain disease featuring elevated IFN-γ levels, blood–brain barrier leakage, and/or T cell infiltration, well before neurodegeneration occurs.
论文信息：
论文题目：Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ
期刊名称：PNAS
时间期卷：116 (10) 4637-4642
DOI: 10.1073/pnas.1813562116
产品信息：
货号：CP-010-010
规格：10ml+10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体清除脾脏边缘区巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS：干扰素‑γ预激活小胶质细胞可减慢原位神经元γ振荡。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
Slice Cultures and Exposures.
Wistar rats (Charles River Laboratories) were handled in accordance with the European directive 2010/63/EU and with consent of the animal welfare officers at University of Heidelberg (licenses, T46/14 and T96/15). Hippocampal slice cultures were prepared from 9- to 10-d-old pups in sterile conditions and maintained on Biopore membranes at the interface between serum-containing culture medium (4 mM glucose) and humidified normal atmosphere enriched with 5% (vol/vol) CO2 (36.5 °C) . Cell culture materials were certified free of endotoxin and IFN-γ. Chemical depletion of microglia was achieved with liposome-encapsulated clodronate (Liposoma B.V.) . Exposures to recombinant IFN-γ (PeproTech), 1400W (Sigma-Aldrich), and LPS (Enzo Life Sciences) were done in the dark.
巨噬细胞清除材料和方法文献截图：
