中文摘要：
Ⅱ型干擾素（IFN?γ）是一種促炎型T淋巴細胞細胞因子。在病理條件下復雜的小膠質細胞活化過程中，它可對中樞神經系統駐留巨噬細胞 —— 小膠質細胞發揮預激活作用。預激活通常會使小膠質細胞在受到二次炎癥刺激時產生放大的應答反應。然而，預激活后的小膠質細胞對于完整皮層組織（原位）內神經元生理功能的影響尚不明確。本研究利用海馬腦片培養模型（即出生后腦實質組織，無白細胞浸潤、不涉及適應性免疫），探究長期IFN?γ 暴露對小膠質細胞的作用。研究重點關注γ頻段（30?70?Hz）快速神經元網絡振蕩。γ振蕩是感知、注意力、記憶等高級腦功能的基礎，并且對代謝應激與氧化應激高度敏感。
IFN?γ可誘導小膠質細胞發生顯著的形態學改變、細胞數量增多，同時適度上調活化標志物（MHC?Ⅱ、CD86、IL?6 與誘導型一氧化氮合酶 iNOS），但并不會上調TNF?α。錐體神經元與小白蛋白陽性抑制性中間神經元的細胞構筑及形態均保持完好。值得注意的是，γ振蕩出現特異性頻率下降，降幅最高可達8?Hz；而IFN?α 或IL?17 處理并不會復制該效應。通過小膠質細胞藥物耗竭實驗與iNOS抑制實驗證實，該節律紊亂由小膠質細胞適度釋放一氧化氮（NO）所介導。
綜上，IFN?γ預激活能夠誘導小膠質細胞明顯增殖與中度活化，進而減慢神經信息處理速度。在以IFN?γ水平升高、血腦屏障滲漏和/或T細胞浸潤為特征的慢性腦部疾病中，該機制可能在神經退行性病變發生之前，就已經參與認知功能損傷。
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.
論文信息：
論文題目：Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ
期刊名稱：PNAS
時間期卷：116 (10) 4637-4642
DOI: 10.1073/pnas.1813562116
產品信息：
貨號：CP-010-010
規格：10ml+10ml
品牌：Liposoma
產地：荷蘭
名稱：Clodronate Liposomes&Control Liposomes
辦事處：靶點科技
Clodronate Liposomes氯膦酸鹽脂質體清除脾臟邊緣區巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS：干擾素?γ預激活小膠質細胞可減慢原位神經元γ振蕩。
Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法：
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.
巨噬細胞清除材料和方法文獻截圖：
