Sleep loss disrupts Arc expression in dentate gyrus neurons.

Sleep loss disrupts Arc expression in dentate gyrus neurons.
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DOI:
10.1016/j.nlm.2018.04.006
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发表时间:
2019-04
影响因子:
2.7
通讯作者:
Aton SJ
Aton SJ
中科院分区:
心理学4区
文献类型:
--
作者:
Delorme JE;Kodoth V;Aton SJ

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睡眠不足影响认知的许多方面,海马体中发生的记忆巩固过程似乎特别容易受到睡眠不足的影响。即时早期基因Arc在突触可塑性和记忆形成中起着重要作用,其表达会因睡眠而改变。在这里,使用各种技术,我们的特点是短暂的(3小时)睡眠与睡眠剥夺(SD)的影响,在小鼠海马和皮层的Arc mRNA和Arc蛋白的表达。通过比较成熟的Arc mRNA与未剪接的前体mRNA的相对丰度,我们看到证据表明,在SD期间,在整个皮质中Arc的增加,而不是海马,反映了从头转录。SD期间海马中的弧增加并不伴随着前mRNA水平的变化,这表明mRNA稳定性的增加而不是转录驱动了这种变化。使用原位杂交(连同行为观察,以量化睡眠量),我们发现,在背侧海马,SD影响最小的弧mRNA的表达,并减少齿状回(DG)颗粒细胞表达弧的数量。这与邻近的皮质区域相反,其显示SD后神经元Arc表达的大幅增加。使用免疫组织化学,我们发现,Arc蛋白表达也受到不同的影响,在皮层和DG与SD -而更多的皮层神经元Arc+,较少的DG颗粒细胞Arc+,相对于相同的区域在睡眠小鼠。这些数据表明,关于可塑性调节基因的表达,睡眠(和SD)可以在海马和皮质区有不同的影响。这可能提供了一个线索,关于表现的敏感性依赖于校园的任务赤字后,即使是短暂的睡眠不足。
Sleep loss affects many aspects of cognition, and memory consolidation processes occurring in the hippocampus seem particularly vulnerable to sleep loss. The immediate-early gene Arc plays an essential role in both synaptic plasticity and memory formation, and its expression is altered by sleep. Here, using a variety of techniques, we have characterized the effects of brief (3-h) periods of sleep vs. sleep deprivation (SD) on the expression of Arc mRNA and Arc protein in the mouse hippocampus and cortex. By comparing the relative abundance of mature Arc mRNA with unspliced pre-mRNA, we see evidence that during SD, increases in Arc across the cortex, but not hippocampus, reflect de novo transcription. Arc increases in the hippocampus during SD are not accompanied by changes in pre-mRNA levels, suggesting that increases in mRNA stability, not transcription, drives this change. Using in situ hybridization (together with behavioral observation to quantify sleep amounts), we find that in the dorsal hippocampus, SD minimally affects Arc mRNA expression, and decreases the number of dentate gyrus (DG) granule cells expressing Arc. This is in contrast to neighboring cortical areas, which show large increases in neuronal Arc expression after SD. Using immunohistochemistry, we find that Arc protein expression is also differentially affected in the cortex and DG with SD - while larger numbers of cortical neurons are Arc+, fewer DG granule cells are Arc+, relative to the same regions in sleeping mice. These data suggest that with regard to expression of plasticity-regulating genes, sleep (and SD) can have differential effects in hippocampal and cortical areas. This may provide a clue regarding the susceptibility of performance on hippocampus-dependent tasks to deficits following even brief periods of sleep loss.
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