Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation.
Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation.
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DOI：
10.1186/s12974-017-0998-z
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发表时间：
2017-11-15
影响因子：
9.3
通讯作者：
Panjwani U
中科院分区：
文献类型：
--
作者：
Wadhwa M;Prabhakar A;Ray K;Roy K;Kumari P;Jha PK;Kishore K;Kumar S;Panjwani U
睡眠不足（SD）会导致认知障碍。神经炎症可能是其中的一个重要因素。大脑局部促炎细胞因子的增加会导致认知缺陷，但 SD 条件下影响的程度并不明显。小胶质细胞激活可能通过调节神经元细胞增殖、分化和脑源性神经元因子 (BDNF) 水平参与 SD 诱导的认知障碍。本研究旨在评估米诺环素通过其抗炎和神经保护作用改善 SD 期间空间记忆衰退的可能有益作用。我们仔细研究了米诺环素对与神经胶质细胞（小胶质细胞和星形胶质细胞）活性相关的炎症细胞因子水平的影响，以及对 SD 期间行为功能至关重要的神经发生标记物。使用自动摇笼装置剥夺体重 230-250 克的雄性 Sprague-Dawley 大鼠 48 小时睡眠。在使用和不使用米诺环素的 SD 完成后立即使用 MWM 装置测试空间记忆。对动物实施安乐死，收集血液，并提取大脑用于神经炎症和神经发生研究。这组实验还使用替莫唑胺（一种神经发生阻滞剂）进行。米诺环素治疗增加了体重、食物摄入量和空间记忆能力，但在 SD 期间下降。它减少了海马和血浆中的促炎细胞因子并增加了抗炎细胞因子水平，并抑制了海马中的反应性神经胶质增生，这通过改善细胞计数、形态和免疫反应性来证明。此外，米诺环素的施用促进了不同阶段的神经发生：增殖（BrdU、Ki-67）、分化（DCX）细胞和生长因子（BDNF）。然而，SD 期间未观察到成熟度 (NeuN) 发生显着变化。此外，在 SD 期间服用替莫唑胺后，与行为、炎症和神经发生相关的分子受到更大的影响，而米诺环素治疗可以恢复这些变化。我们观察到 SD 期间神经发生与小胶质细胞激活、细胞因子水平和空间记忆存在显着相关性。本研究表明，SD 引起的空间记忆、神经细胞增殖、分化和 BDNF 水平下降可归因于神经炎症分子的上调，而米诺环素可能是抵消这些变化的有效干预措施。小胶质细胞激活参与 SD 诱导的炎症分子、神经发生和空间记忆的变化。 本文的在线版本 (10.1186/s12974-017-0998-z) 包含补充材料，可供授权用户使用。
Sleep deprivation (SD) leads to cognitive impairment. Neuroinflammation could be a significant contributing factor in the same. An increase in regional brain pro-inflammatory cytokines induces cognitive deficits, however, the magnitude of the effect under SD is not apparent. It is plausible that microglia activation could be involved in the SD-induced cognitive impairment by modulation of neuronal cell proliferation, differentiation, and brain-derived neuronal factor (BDNF) level. The present study aimed to evaluate the possible beneficial effect of minocycline in amelioration of spatial memory decline during SD by its anti-inflammatory and neuroprotective actions. We scrutinized the effect of minocycline on the inflammatory cytokine levels associated with glial cells (microglia and astrocytes) activity and neurogenesis markers crucial for behavioral functions during SD. Male Sprague-Dawley rats weighing 230–250 g were sleep deprived for 48 h using automated cage shaking apparatus. The spatial memory was tested using MWM apparatus immediately after completion of SD with and without minocycline. The animals were euthanized, blood was collected, and brain was extracted for neuroinflammation and neurogenesis studies. The set of experiments were also conducted with use of temozolomide, a neurogenesis blocker. Minocycline treatment increased the body weight, food intake, and spatial memory performance which declined during SD. It reduced the pro-inflammatory and increased the anti-inflammatory cytokine levels in hippocampus and plasma and inhibited the reactive gliosis in the hippocampus evidenced by improved cell count, morphology, and immunoreactivity. Additionally, minocycline administration promoted neurogenesis at different stages: proliferation (BrdU, Ki-67), differentiation (DCX) cells and growth factor (BDNF). However, no significant change was observed in maturation (NeuN) during SD. In addition, molecules related to behavior, inflammation, and neurogenesis were shown to be more affected after temozolomide administration during SD, and changes were restored with minocycline treatment. We observed a significant correlation of neurogenesis with microglial activation, cytokine levels, and spatial memory during SD. The present study demonstrated that the SD-induced decline in spatial memory, neuronal cells proliferation, differentiation, and BDNF level could be attributed to upregulation of neuroinflammatory molecules, and minocycline may be an effective intervention to counteract these changes. Microglial activation is involved in SD-induced changes in inflammatory molecules, neurogenesis, and spatial memory. The online version of this article (10.1186/s12974-017-0998-z) contains supplementary material, which is available to authorized users.
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影响因子：
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