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(fù)雜的小膠質(zhì)細胞活化過程中，它可對中樞神經(jīng)系統(tǒng)駐留巨噬細胞 —— 小膠質(zhì)細胞發(fā)揮預(yù)激活作用。預(yù)激活通常會使小膠質(zhì)細胞在受到二次炎癥刺激時產(chǎn)生放大的應(yīng)答反應(yīng)。然而，預(yù)激活后的小膠質(zhì)細胞對于完整皮層組織（原位）內(nèi)神經(jīng)元生理功能的影響尚不明確。本研究利用海馬腦片培養(yǎng)模型（即出生后腦實質(zhì)組織，無白細胞浸潤、不涉及適應(yīng)性免疫），探究長期IFN?γ 暴露對小膠質(zhì)細胞的作用。研究重點關(guān)注γ頻段（30?70?Hz）快速神經(jīng)元網(wǎng)絡(luò)振蕩。γ振蕩是感知、注意力、記憶等高級腦功能的基礎(chǔ)，并且對代謝應(yīng)激與氧化應(yīng)激高度敏感。

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(chǎn)品信息：

貨號：CP-010-010

規(guī)格：10ml+10ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除脾臟邊緣區(qū)巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS：干擾素?γ預(yù)激活小膠質(zhì)細胞可減慢原位神經(jīng)元γ振蕩。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)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：