Sleep deprivation under sustained hypoxia protects against oxidative stress

Abstract

We previously showed that total sleep deprivation increased antioxidant responses in several rat brain regions. We also reported that chronic hypoxia enhanced antioxidant responses and increased oxidative stress in rat cerebellum and pons, relative to normoxic conditions. In the current study, we examined the interaction between these two parameters (sleep and hypoxia). We exposed rats to total sleep deprivation under sustained hypoxia (SDSH), and compared changes in antioxidant responses and oxidative stress markers, in the neocortex, hippocampus, brainstem and cerebellum, to those in control animals left undisturbed under either sustained hypoxia (UCSH) or normoxia (UCN). We measured changes in total nitrite levels, as an indicator of nitric oxide (NO) production, superoxide dismutase (SOD) activity and total glutathione (GSHt) levels as markers of antioxidant responses and levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls as signs of lipid and protein oxidation products, respectively. We found that acute (6h) SDSH increased NO production in the hippocampus and increased GSHt levels in the neocortex, brainstem and cerebellum, while decreasing hippocampal lipid oxidation. Additionally, we observed increased hexokinase (HK) activity in the neocortex of SDSH rats compared to UCSH rats, suggesting that elevated glucose metabolism may be one potential source of the enhanced free radicals produced in this brain region. We conclude that short term insomnia under hypoxia may serve as an adaptive response to prevent oxidative stress.

The short- and long-term proteomic effects of sleep deprivation on the cortical and thalamic synapses

“…6) among which 7 protein showed level increase. This is in agreement with previous examinations and theories, that concluded antioxidant responses after sleep deprivation, as a consequence of the higher metabolic rate related to prolonged wakefulness (Reimund, 1994; Brown and Naidoo, Ramanathan et al, 2010;Ramanathan and Siegel, 2011). This result draws attention on a high level of impairment in the oxidative homeostasis which is even more pronounced later after sleep deprivation termination.…”

Sleep Deprivation and Oxidative Stress in Animal Models: A Systematic Review

“…On the other hand, to block SWS, it was found that the most reported protocol is the total sleep deprivation (TSD) procedure [ 29 , 36 , 38 , 39 , 53 – 55 ]. The TSD data is summarized in Table 2 .…”

“…For example, 12 articles of mice under PSD procedures [ 27 , 40 , 41 , 43 – 47 , 49 – 52 ] and 13 papers of rats after PSD methods [ 28 , 30 – 35 , 37 , 42 , 48 , 56 – 58 ] were analyzed. However, TSD protocols were described exclusively in rats [ 29 , 36 , 38 , 39 , 53 – 55 ].…”

“…Moreover, 13 papers were focused on the antioxidant measure on the whole brain [ 35 , 40 – 48 , 50 , 51 , 58 ], 2 articles described the issue on the striatum [ 27 , 42 ], 17 reports included the hippocampus [ 27 – 29 , 31 – 38 , 42 , 49 , 52 , 54 , 55 , 57 ], 12 papers reported the antioxidants in the cortex [ 27 , 28 , 30 , 34 , 36 – 38 , 42 , 53 , 55 , 57 , 58 ], 1 article was aimed at the amygdala [ 34 ], 4 articles addressed the issue on hypothalamus [ 42 , 55 – 57 ], 2 reported papers described it at the thalamus [ 42 , 57 ], 4 reports mentioned the brainstem [ 36 , 38 , 42 , 55 ], 4 articles reported the antioxidant activity in the cerebellum [ 36 , 38 , 55 , 57 ], 1 paper demonstrated the link in the pons [ 57 ], and finally 1 report published the association among antioxidant levels and forebrain [ 38 ].…”

Cerebral lactate dynamics across sleep/wake cycles

“…Suppression of firing of hippocampal pyramidal cells by lactate has been attributed to changes in redox status (Gilbert et al, 2006 ). Enforced wakefulness is characterized by a significant oxidative burden relative to sleep (Silva et al, 2004 ; Cirelli, 2006 ; Ramanathan et al, 2010 ; Ramanathan and Siegel, 2011 ). Manipulation of oxidative stress-related pathways affects sleep wake cycles (Honda et al, 1994 ; Inoué et al, 1995 ; Kimura et al, 1998 ; Ikeda et al, 2005 ).…”