Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060, USA.
Neurobiol Dis. 2012 Dec;48(3):348-55. doi: 10.1016/j.nbd.2012.06.022. Epub 2012 Jul 7.
Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients.
住院患者可能会出现认知功能下降，其机制仍在很大程度上尚未确定。住院患者经常会出现睡眠障碍，而神经炎症可导致学习和记忆损伤。因此，我们着手研究睡眠障碍是否会在啮齿动物中引起神经炎症和学习记忆损伤。研究使用了 5 至 6 个月大的野生型 C57BL/6J 雄性小鼠。将这些小鼠置于晃动的笼子中 24 小时，每个笼子中都有两个滚动球。在睡眠干扰后 1 天和 7 天，使用恐惧条件测试来测试小鼠的学习和记忆功能。还测定了小鼠脑组织中的神经炎症。在睡眠干扰后 1 天和 7 天的恐惧条件测试中，24 小时的睡眠干扰降低了评估海马体依赖性学习和记忆的情境测试中的冻结时间，但不降低评估海马体独立性学习和记忆的音调测试中的冻结时间。睡眠干扰增加了促炎细胞因子 IL-6 的水平，并在小鼠海马体中引起小神经胶质细胞激活，但在皮质中没有引起。这些结果表明，睡眠干扰会导致小鼠海马体中的神经炎症，并损害小鼠的海马体依赖性学习和记忆。在进一步的研究中，这些发现表明，睡眠干扰引起的神经炎症和学习记忆损伤可能是导致住院患者认知功能下降的原因之一。
