Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation
Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation
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DOI：
10.1111/j.1365-2869.2009.00799.x
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Meerlo, Peter
中科院分区：
文献类型：
--
作者：
Hagewoud, Roelina;Havekes, Robbert;Meerlo, Peter
睡眠对大脑功能和认知能力很重要.睡眠剥夺（SD）可能会影响随后的学习能力和形成新记忆的能力，特别是在依赖于校园的任务的情况下。在本研究中，我们研究了是否SD 6或12小时在正常的休息阶段学习前影响海马依赖的工作记忆的小鼠。此外，我们确定了SD对海马谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体及其调节途径的影响，这是至关重要的参与工作记忆。SD后12 h，但6 h后尚未，空间工作记忆在一个新的手臂识别任务显着受损。这种缺陷不太可能是由于压力，因为SD后的皮质酮水平在各组之间没有显著差异。与认知功能的变化平行，我们发现12 h SD显著降低了海马AMPA受体GluR 1-S845位点的磷酸化，这对于受体掺入膜中非常重要。SD不影响环AMP依赖性蛋白激酶A（PKA）或磷酸酶钙调神经磷酸酶（CaN）的蛋白水平，调节GluR 1磷酸化。然而，SD确实降低了支架分子A-激酶锚定蛋白150（AKAP 150）的表达，AKAP 150结合并部分控制PKA和CaN的作用。总之，在正常的休息阶段相对较短的SD可能会影响空间工作记忆的小鼠海马AMPA受体功能的变化，通过AKAP 150水平的变化。总之，这些发现提供了进一步了解SD诱导海马功能障碍和记忆障碍的可能机制。
P>Sleep is important for brain function and cognitive performance. Sleep deprivation (SD) may affect subsequent learning capacity and ability to form new memories, particularly in the case of hippocampus-dependent tasks. In the present study we examined whether SD for 6 or 12 h during the normal resting phase prior to learning affects hippocampus-dependent working memory in mice. In addition, we determined effects of SD on hippocampal glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and their regulatory pathways, which are crucially involved in working memory. After 12 h SD, but not yet after 6 h, spatial working memory in a novel arm recognition task was significantly impaired. This deficit was not likely due to stress as corticosterone levels after SD were not significantly different between groups. In parallel with the change in cognitive function, we found that 12 h SD significantly reduced hippocampal AMPA receptor phosphorylation at the GluR1-S845 site, which is important for incorporation of the receptors into the membrane. SD did not affect protein levels of cyclic-AMP-dependent protein kinase A (PKA) or phosphatase calcineurin (CaN), which regulate GluR1 phosphorylation. However, SD did reduce the expression of the scaffolding molecule A-kinase anchoring protein 150 (AKAP150), which binds and partly controls the actions of PKA and CaN. In conclusion, a relatively short SD during the normal resting phase may affect spatial working memory in mice by reducing hippocampal AMPA receptor function through a change in AKAP150 levels. Together, these findings provide further insight into the possible mechanism of SD-induced hippocampal dysfunction and memory impairment.