Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.
Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone.
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DOI：
10.3389/fncel.2016.00132
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发表时间：
2016
影响因子：
5.3
通讯作者：
Gonzalez-Castañeda RE
中科院分区：
文献类型：
--
作者：
Soto-Rodriguez S;Lopez-Armas G;Luquin S;Ramos-Zuñiga R;Jauregui-Huerta F;Gonzalez-Perez O;Gonzalez-Castañeda RE
睡眠剥夺会影响空间记忆和齿状回的增殖。目前尚不清楚这些有害影响是否会长期存在。本研究的目的是观察SD后21天神经祖细胞的增殖、分化、成熟及空间记忆的变化。60日龄雄性Balb/C小鼠暴露于72小时REM-SD。在SD或对照组后的第0、14和21天，评估海马的空间记忆、细胞命运、凋亡和胰岛素样生长因子1受体（IGF-1R）的表达水平。经过21天的恢复期后，用巴恩斯迷宫评估记忆表现，我们发现SD小鼠的记忆功能明显受损（94.0±10.2 s vs. 25.2±4.5 s; p < 0.001）。SD组BrdU+细胞数量在第14天（对照组= 1.6±0.1，SD小鼠= 1.2±0.1个细胞/场，p = 0.001）和第21天（对照组= 0.2±0.03，SD小鼠= 0.1±0.02个细胞/场，p < 0.001）均显著减少。差异有统计学意义（1.4±0.1个细胞/场vs 0.9±0.1个细胞/场，p = 0.003）。与对照组（0.19±0.03 TUNEL+细胞/场p < 0.001）相比，SD后第14天细胞凋亡（0.53±0.06 TUNEL+细胞/场）和SD后第21天（SD小鼠0.53±0.15 TUNEL+细胞/场，p = 0.035）显著增加。第0天，SD动物IGF-1R表达量（64.6±12.2单位）较对照组（102.0±9.8单位，p = 0.043）显著降低。然而，在SD后第14天和第21天，差异无统计学意义。综上所述，单次暴露于SD 72小时可诱导持续至少3周的有害影响。这些变化的特征是空间记忆障碍、海马BrdU+细胞数量减少和持续的凋亡率。相反，IGF-1R表达的变化似乎是一个短暂的事件。睡眠剥夺影响空间记忆和齿状回的增殖。迄今为止，尚不清楚这些有害影响是否会长期持续。我们分析了21天恢复性睡眠后睡眠剥夺对海马体的影响。我们的研究结果表明，在睡眠恢复后，SD的有害影响至少可以观察到2周，表现为记忆能力下降，海马细胞成分变化和长时间的高凋亡率。
Sleep deprivation (SD) affects spatial memory and proliferation in the dentate gyrus. It is unknown whether these deleterious effects persist in the long run. The aim of this study was to evaluate the proliferation, differentiation and maturation of neural progenitors as well as spatial memory 21 days after suffering SD. Sixty-day old male Balb/C mice were exposed to 72-h REM-SD. Spatial memory, cell fate, apoptosis and expression levels of insulin-like growth factor 1 receptor (IGF-1R) were evaluated in the hippocampus at 0, 14, and 21 days after SD or control conditions. After 21-days recovery period, memory performance was assessed with the Barnes maze, we found a significant memory impairment in SD mice vs. control (94.0 ± 10.2 s vs. 25.2 ± 4.5 s; p < 0.001). The number of BrdU+ cells was significantly decreased in the SD groups at day 14 (controls = 1.6 ± 0.1 vs. SD mice = 1.2 ± 0.1 cells/field; p = 0.001) and at day 21 (controls = 0.2 ± 0.03 vs. SD mice = 0.1 ± 0.02 cells/field; p < 0.001). A statistically significant decrease was observed in neuronal differentiation (1.4 ± 0.1 cells/field vs. 0.9 ± 0.1 cells/field, p = 0.003). Apoptosis was significantly increased at day 14 after SD (0.53 ± 0.06 TUNEL+ cells/field) compared to controls (0.19 ± 0.03 TUNEL+ cells/field p < 0.001) and at 21-days after SD (SD mice 0.53 ± 0.15 TUNEL+ cells/field; p = 0.035). At day 0, IGF-1R expression showed a statistically significant reduction in SD animals (64.6 ± 12.2 units) when compared to the control group (102.0 ± 9.8 units; p = 0.043). However, no statistically significant differences were found at days 14 and 21 after SD. In conclusion, a single exposition to SD for 72-h can induce deleterious effects that persist for at least 3 weeks. These changes are characterized by spatial memory impairment, reduction in the number of hippocampal BrdU+ cells and persistent apoptosis rate. In contrast, changes IGF-1R expression appears to be a transient event. Highlight Sleep deprivation affects spatial memory and proliferation in the dentate gyrus. To date it is unknown whether these deleterious effects are persistent over a long period of time. We analyzed the effects of sleep deprivation in the hippocampus after 21 days of recovery sleep. Our findings indicate that after sleep recovery, the detrimental effects of SD can be observed for at least 2 weeks, as shown by a reduction in memory performance, changes in the hippocampal cellular composition and higher apoptotic rate over a long period of time.