Hydrogen Sulfide Reverses Sleep Deprivation-induced Depressive- And Anxiety-like Behaviors In Rats Via Inhibiting Neuroinflammation

[Backgroud and Objective] Recent studies have shown that sleep deprivation(SD) increases the risk of depression and anxiety. Neuroinflammation plays an important role in the development of depression. Regulating neuroinflammation is a potential treatment of depression. Hydrogen sulfide(H2S), a new type of neuromodulator and gaseous mediator, play a important role in nerve-protection, regulation of synaptic plasticity and inhibiting neuroinflammation. Previous work in our laboratory have showed that H2 S can alleviate diabetes-related and acute stress-induced depressive- and anxiety-like behaviors in rats. Therefore, the objectives of this study were to(1) determine whether SD can induce depressive- and anxiety-like behaviors as well as promote neuroinflammation in rats,(2) explore whether H2 S can reverse SD-induced depressive- and anxiety-like behaviors, and if the mechanism is involved in regulating neuroinflammation?[Methods] Rats were subjected to SD by the modified multiple platform method(MMPM). Novelty-suppressed feeding test(NSFT), forced swimming test(FST) and tail suspension test(TST) were used to detect depressive-like behaviors, and elevated plus-maze test(EPMT) was used to measure anxiety-like behaviors of rats. Locomotor activity was conducted to detect activity level. The contents of proinflammatory cytokines(IL-1β, IL-6 and TNF-α), anti-inflammatory cytokines(IL-4 and IL-10), as well as fractalkine(CCL2 and CX3CL1) in brain were determined by ELISA. The levels of macrophages and activated astrocytes in brian were detected by immunofluorescence assay.[Results] 1. SD induces depressive- and anxiety-like behaviors in rats. Compared with control group, 72 h-SD increased the latency to the first bite of food in NSFT, increased duration of immobility and decreased duration of climbing in FST, spent more time to being still in TST, and decreased the time spent in the open arms as well as the percentage of entries into the open arms. Meanwhile, no obvious difference was found in locomotor activity. These results indicate that SD can induce depressive-like and anxiety-like behaviors in rats. 2. SD promotes neuroinflammation in rats’ brian. Compared with control group, SD increased the contents of proinflammatory cytokines(IL-1β, IL-6 and TNF-α) and decreased the contents of anti-inflammatory cytokines(IL-4 and IL-10) in rats’ brian. In addition, the levels of macrophages and activated astrocytes as well as fractalkine(CCL2 and CX3CL1) in brain were increased by SD. These results demonstrate that SD can promote neuroinflammation in rats’ brian.3. H2 S reverses SD-induced depressive- and anxiety-like behaviors in rats. Na HS(30 and 100 μmol/Kg/d, ip, 10 d), a H2 S donor, significantly decreased the latency to the first bite of food in NSFT, decreased the duration of immobility while increased the duration of climbing in FST of SD rats. Meanwhile, Na HS(30 and 100 μmol/Kg/d) markedly shortened the duration of immobility in TST of SD rats. These results prove that H2 S can alleviate SD-induced depressive-like behaviors in rats. In addition, Na HS(30 and 100 μmol/Kg/d) significantly increased the time spent in the open arms as well as the percentage of entries into the open arms in EPMT of SD rats, which show that H2 S can alleviate SD-induced anxiety-like behaviors in rats. However, there is no obvious difference in locomotor activity among all groups. 4. H2 S rescues SD-induced neuroinflammation in rats’ brain. Na HS(30 and 100 μmol/Kg/d, ip, 10 d) significantly abolished SD-induced increase in proinflammatory cytokines(IL-1β, IL-6 and TNF-α) and decrease in anti-inflammatory cytokines(IL-4 and IL-10). Meanwhile, Na HS markedly attenuated SD-induced increase in the amount of macrophages and activated astrocytes, as well as the level of fractalkine(CCL2 and CX3CL1) in rats’ brain. These results indicate that H2 S can rescue SD-induced neuroinflammation in rats’ brain.[Conclusion] 1. SD can induce depressive- and anxiety-like behaviors as well as promote neuroinflammation in rats.2. H2 S can reverse SD-induced depressive- and anxiety-like behaviors via inhibiting neuroinflammation.