Chronic sleep restriction (CSR) negatively impacts brain functions. Whether microglia, the brain's resident immune cells, play any role is unknown. We studied microglia responses to CSR using a rat model featuring slowly rotating wheels (3 h on/1 h off), which was previously shown to induce both homeostatic and adaptive responses in sleep and attention. Adult male rats were sleep restricted for 27 or 99 h. Control rats were housed in locked wheels. After 27 and/or 99 h of CSR, the number of cells immunoreactive for the microglia marker ionized calcium-binding adaptor molecule-1 (Iba1) and the density of Iba1 immunoreactivity were increased in 4/10 brain regions involved in sleep/wake regulation and cognition, including the prelimbic cortex, central amygdala, perifornical lateral hypothalamic area, and dorsal raphe nucleus. CSR neither induced mitosis in microglia (assessed with bromodeoxyuridine) nor impaired blood-brain barrier permeability (assessed with Evans Blue). Microglia appeared ramified in all treatment groups and, when examined quantitatively in the prelimbic cortex, their morphology was not affected by CSR. After 27 h, but not 99 h, of CSR, mRNA levels of the anti-inflammatory cytokine interleukin-10 were increased in the frontal cortex. Pro-inflammatory cytokine mRNA levels (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were unchanged. Furthermore, cortical microglia were not immunoreactive for several pro- and anti-inflammatory markers tested, but were immunoreactive for the purinergic P2Y12 receptor. These results suggest that microglia respond to CSR while remaining in a physiological state and may contribute to the previously reported homeostatic and adaptive responses to CSR.

中文翻译：

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慢性睡眠受限大鼠模型中小胶质细胞的稳态

慢性睡眠限制 (CSR) 会对大脑功能产生负面影响。小胶质细胞（大脑的常驻免疫细胞）是否发挥任何作用尚不清楚。我们使用具有缓慢旋转轮子（开启 3 小时/关闭 1 小时）的大鼠模型研究了小胶质细胞对 CSR 的反应，该模型先前已被证明可在睡眠和注意力中诱导稳态和适应性反应。成年雄性大鼠被限制睡眠 27 或 99 小时。对照大鼠被安置在锁定的轮子中。在 CSR 27 和/或 99 小时后，4/10 参与睡眠/觉醒调节的大脑区域中，对小胶质细胞标记物离子钙结合接头分子-1（Iba1）具有免疫反应性的细胞数量和 Iba1 免疫反应性密度增加和认知，包括前缘皮层、中央杏仁核、眶周外侧下丘脑区和中缝背核。CSR 既不诱导小胶质细胞有丝分裂（用溴脱氧尿苷评估），也不损害血脑屏障通透性（用伊文思蓝评估）。小胶质细胞在所有治疗组中都出现分支，并且在前边缘皮层中进行定量检查时，它们的形态不受 CSR 的影响。CSR 27 小时后，而非99 小时后，额叶皮质中抗炎细胞因子白细胞介素10 的mRNA 水平增加。促炎细胞因子 mRNA 水平（肿瘤坏死因子-α、白介素-1β 和白介素-6）没有变化。此外，皮质小胶质细胞对几种测试的促炎和抗炎标记物没有免疫反应，但对嘌呤能 P2Y12 受体有免疫反应。