Rapid Eye Movement Sleep Deprivation Produces Long-Term Detrimental Effects in Spatial Memory and Modifies the Cellular Composition of the Subgranular Zone

Abstract

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.

Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

“…Recent findings showed that the sleep deprivation has a delayed effect on the cell differentiation in the SGZ and increases the apoptosis rate in the hippocampal CA1 and CA3 regions [76]. Our data indicate that exogenous administration of melatonin restores the tissue levels of this hormone in the hippocampus and increases the number of neural precursors and reveals a neuroprotective effect of melatonin against the deleterious consequences of REMSD.…”

Permanent Whisker Removal Reduces the Density of c-Fos+ Cells and the Expression of Calbindin Protein, Disrupts Hippocampal Neurogenesis and Affects Spatial-Memory-Related Tasks

“…These alterations may be due to functional variations (less neuronal activity) or structural changes (less neuronal production). To determine whether the whisker elimination affected the neuronal production in the SGZ, we injected BrdU 2 h before sacrifice ( n = 5 mice per group) and studied the proliferation rate of hippocampal neural progenitors (Soto-Rodriguez et al, 2016 ; Figures 3A–K ). We quantified the number of BrdU+ cells in the SGZ and found a statistically significant reduction in WD mice (Mdn = 21.8 cells/mm 2 of SGZ area, IQR: 19.2–30.9) as compared with the control group (Mdn = 45.2 cells/mm 2 of SGZ area, IQR: 35.4–52.4; U = 6, P = 0.001; Figure 3H ).…”

“…Additionally, pharmacologically induced vibrissae paralysis did not affect the animal’s ability to learn (Patarroyo et al, 2017 ). We used the Barnes maze to evaluate both spatial memory and navigation (Barnes, 1979 ; Soto-Rodriguez et al, 2016 ). Our data indicated that the permanent deprivation of whiskers notably impairs the acquisition of spatial memory, as shown by longer latencies spent to find the goal holes.…”

“…Our data indicated that the permanent deprivation of whiskers notably impairs the acquisition of spatial memory, as shown by longer latencies spent to find the goal holes. A possible explanation for some inconsistent findings between Morris and Barnes mazes in WD models may be due to the solving strategy for the Barnes maze requires both visual and tactile skills (Barnes, 1979 ; Soto-Rodriguez et al, 2016 ). Thus, Barnes may be a more sensitive behavioral paradigm to evaluate memory integration that is required to create spatial maps (Grion et al, 2016 ).…”

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure

“…There are 2 possible explanations for the increase of corticosterone and a subsequent decrease of this molecule under CUS that we find. The first implies negative feedback on the HPA axis that remains even under the hyperactivity that is present after CUS [ 36 ] and second, a decompensation where the adrenal cortex cannot meet the demand for glucocorticoids and it decreases even though there is a high concentration of the hormone adrenocorticotropin (ACTH) [ 37 ]. Other pieces of evidence propose the measurement of the relative weight of the adrenal glands as an indicator of dysregulation of the HPA axis in various models of depression [ 32 ].…”