Isorhamnetin Ameliorates Sleep Deprivation Induced Acognitive Dysfunction By Reducing Oxidative Stress,Inflammation And Neuronal Apoptosis In Mice

Objective:Sleep deprivation(SD)could cause a sequence of neurobehavioral deficits and physiological consequences.Isorhamnetin(ISOR)has been verified to have neuronal protective,anti-inflammatory and anti-oxidative effects.This article aimed to explore the mechanism under the neuroprotective effect of ISOR against 72h SD-induced anxiety like behavior,oxidative stress,neuroinflammation in mice.Methods:Male KunMing mice(n=60,22-30 g,5 weeks)were randomly divided into four groups each consisting 15 mice:control group(Control),sleep deprivation group(SD),Isorhamnetin group(ISOR),Isorhamnetin+SD group(ISOR+SD).The ameliorating effect of ISOR on SD-induced learning and memory impairment was evaluated by open field test(OFT)and morris water maze tests(MWM).After the behavioral tests,antioxidant effects were detected by malondialdehyde(MDA),superoxide dismutase(SOD),reduced glutathione(GSH)and catalase(CAT)assays.The level of tumor necrosis factor-a(TNFa)and interleukin-1?(IL-1?)both in serum and brain homogenates were detected by ELISA.Expressions of Bcl-2,Bax were also detected along with JNK,P38 and ERK phosphorylation by western blot.HE staining and TUNEL assays were used to observe the neuron pathologic morphology and apoptosis caused by SD.Results:There was a significant reduction in the number of crossings and rearings in SD group mice compared with the control group(P<0.01).However,ISOR treatment groups showed higher locomotor and exploration activity(P<0.01).SD group showed a higher escape latency compared with the control group(P<0.05).However,the ISOR group showed remarkable ameliorating effects on SD-induced learning and memory impairment(P<0.01).Compared with Control group,SD group could increased the oxidative stress,neuroinflammation and the neuronal apoptosis,in contrast,ISOR treatment on SD could reduced oxidative stress,neuroinflammation and the neuronal apoptosis.Conclusion:The results suggest that ISOR could improve cognitive functions induced by 72h SD by reducing the anxiety like behavior,oxidative stress,neuroinflammation and the neuronal apoptosis.