Eiland, M. M. et al. Increases in amino-cupric-silver staining of the supraoptic nucleus after sleep deprivation. Brain Res. 945, 1-8
University of Chicago, Chicago, Illinois, United States Brain Research
(Impact Factor: 2.84).
07/2002; 945(1):1-8. DOI: 10.1016/S0006-8993(02)02448-4
Sleep deprived rats undergo a predictable sequence of physiological changes, including changes in skin condition, increased energy expenditure, and altered thermoregulation. Amino-cupric-silver staining was used to identify sleep deprivation related changes in the brain. A significant increase in staining was observed in the supraoptic nucleus (SON) of the hypothalamus of rats with high sleep loss (>45 h) vs. their yoked controls. Follow-up experiments showed that staining was not significantly different in rats sleep deprived for less than 45 h, suggesting that injurious sleep deprivation-related processes occur above a threshold quantity of sleep loss. These anatomical changes suggest that the effects of sleep deprivation may be related to protein metabolism in certain brain regions.
Available from: Paul J Lucassen
- "Moreover, measurements of the cellular subregions suggest that the volume reduction was not limited to the DG but may have included the non-neurogenic CA regions as well. Since there is little to no evidence for massive neuronal death even after prolonged total sleep deprivation (Cirelli et al., 1999; Eiland et al., 2002), it seems more likely that part of the volume reduction was caused by a decrease in the size of neuronal cell bodies and dendritic arborizations or by changes in the number and size of glia cells. "
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ABSTRACT: Sleep loss strongly affects brain function and may even predispose susceptible individuals to psychiatric disorders. Since a recurrent lack of sleep frequently occurs during adolescence, it has been implicated in the rise in depression incidence during this particular period of life. One mechanism through which sleep loss may contribute to depressive symptomatology is by affecting hippocampal function. In this study, we examined the effects of sleep loss on hippocampal integrity at young age by subjecting adolescent male rats to chronic sleep restriction (SR) for 1 month from postnatal day 30 to 61. They were placed in slowly rotating drums for 20 h per day and were allowed 4 h of rest per day at the beginning of the light phase. Anxiety was measured using an open field and elevated plus maze test, while saccharine preference was used as an indication of anhedonia. All tests were performed after 1 and 4 weeks of SR. We further studied effects of SR on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure hippocampal volume and neurogenesis. Behavior of the SR animals was not affected, except for a transient suppression of saccharine preference after 1 week of SR. Hippocampal volume was significantly reduced in SR rats compared to home cage and forced activity controls. This volume reduction was not paralleled by reduced levels of hippocampal neurogenesis and could neither be explained by elevated levels of glucocorticoids. Thus, our results indicate that insufficient sleep may be a causal factor in the reductions of hippocampal volume that have been reported in human sleep disorders and mood disorders. Since changes in HPA activity or neurogenesis are not causally implicated, sleep disturbance may affect hippocampal volume by other, possibly more direct mechanisms.
Available from: Peter Meerlo
- "One study reported that prolonged total sleep deprivation for 5–14 days had no effect on expression of apoptotic genes and did not increase staining for TUNEL and Fluor-Jade as markers of DNA damage and neuronal degeneration (Cirelli et al., 1999). Another study showed that sleep deprivation for 8–10 days did not increase cell damage in most brain regions as assessed by silver staining, except for a localized increase in the supraoptic nucleus of the hypothalamus (Eiland et al., 2002). A third study showed a temporary increaseintheexpressionofapoptoticmarkers,andanincrease in the number of TUNEL-or silver-stained degenerating cells in several brain areas of rats deprived of rapid eye movement (REM) sleep for 6–10 days (Biwas et al., 2006). "
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ABSTRACT: It has been hypothesized that insufficient sleep may compromise neuronal function and contribute to neurodegenerative processes. While sleep loss by itself may not lead to cell death directly, it may affect the sensitivity to a subsequent neurodegenerative insult. Here we examined the effects of chronic sleep restriction (SR) on the vulnerability of the brain to N-methyl-d-aspartate (NMDA)-induced excitotoxicity. Animals were kept awake 20 h per day and were only allowed to rest during the first 4 h of the light phase, i.e. their normal circadian resting phase. After 30 days of SR all rats received a unilateral injection with a neurotoxic dose of NMDA into the nucleus basalis magnocellularis (NBM). Brains were collected for assessment of damage. In the intact non-injected hemisphere, the number of cholinergic cells in the NBM and the density of their projections in the cortex were not affected by SR. In the injected hemisphere, NMDA caused a significant loss of cholinergic NBM cells and cortical fibres in all animals. However, the loss of cholinergic cells was attenuated in the SR group as compared with the controls. These data suggest that, if anything, SR reduces the sensitivity to a subsequent excitotoxic insult. Chronic SR may constitute a mild threat to the brain that does not lead to neurodegeneration by itself but prepares the brain for subsequent neurotoxic challenges. These results do not support the hypothesis that sleep loss increases the sensitivity to neurodegenerative processes.
Available from: ncbi.nlm.nih.gov
- "In a previous study, however, we found no evidence that prolonged (up to 2 weeks) sleep deprivation may result in cellular damage leading to neuronal degeneration, as measured by Fluoro-Jade staining, and cell death, as detected by the TUNEL method (Cirelli et al., 1999). Another study used the amino-cupric-silver staining method after 8–10 days of sleep loss, and found an increase in degenerating cells only in the supraoptic nucleus of the hypothalamus, but not in cortex or other brain areas (Eiland et al., 2002). In a genome-wide transcriptomic study we also found no signs of upregulation of apoptotic genes after chronic sleep loss (Cirelli et al., 2006). "
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ABSTRACT: Transcriptomic studies have shown that hundreds of genes change their expression levels across the sleep/waking cycle, and found that waking-related and sleep-related mRNAs belong to different functional categories. Proteins, however, rather than DNA or RNA, carry out most of the cellular functions, and direct measurements of protein levels and activity are required to assess the effects of behavioral states on the overall functional state of the cell. Here we used surface-enhanced laser desorption-ionization (SELDI), followed by time-of-flight mass spectrometry, to obtain a large-scale profiling of the proteins in the rat cerebral cortex whose expression is affected by sleep, spontaneous waking, short (6 hours) and long (7 days) sleep deprivation. Each of the 94 cortical samples was profiled in duplicate on 4 different ProteinChip Array surfaces using 2 different matrix molecules. Overall, 1055 protein peaks were consistently detected in cortical samples and 15 candidate biomarkers were selected for identification based on significant changes in multiple conditions (conjunction analysis): 8 "sleep" peaks, 4 "waking" peaks, and 4 "long sleep deprivation" peaks. Four candidate biomarkers were purified and positively identified. The 3353 Da candidate sleep marker was identified as the 30 amino acid C-terminal fragment of rat histone H4. This region encompasses the osteogenic growth peptide, but a possible link between sleep and this peptide remains highly speculative. Two peaks associated with short and long sleep deprivation were identified as hemoglobin alpha1/2 and beta, respectively, while another peak associated with long sleep deprivation was identified as cytochrome C. The upregulation of hemoglobins and cytochrome C may be part of a cellular stress response triggered by even short periods of sleep loss.
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