The Effects Of Chronic Sleep Fragmentation Of Different Durations On AD-like Pathological Changes In The Brain Of Normal Mice

Objective Healthy sleep is essential for maintaining normal cognitive function.This research is to explore the effects of chronic sleep fragmentation of different durations on AD-like pathology in the brain of normal mice.Methods 8-week-old male C57 BL / 6J mice were used to build the chronic sleep fragmentation(SF)model,which last for 1.5 months(1.5m)and 4 months(4m),respectively.The same-age and same-sex non-intervention mice were used as controls.Immunohistochemical staining and Western Blot were used to detect amyloid Aβ1-42,total tau protein,the phosphorylation of tau protein at sites of serine(Ser)396 and threonine(Thr)231 in the cortex and hippocampus.Immunohistochemical staining was used to detect the expression of microglial marker Iba-1 and astrocyte marker GFAP in mouse brain.18F-FDG PET/CT was used to detect the change of brain glucose metabolism in mice of each group.Results 1.1.5m SF and 4m SF mice were not significantly different from control mice on body weight.2.1.5-month and 4-month sleep fragmentation can lead to Aβ1-42 deposition in neurocytes of normal mouse brain.3.The p-tau(Ser396)level of 1.5-month SF mice were significantly higher than the control group in both cortex(P = 0.048)and hippocampus(P = 0.043),while p-tau(Thr231)level was not significantly changed in the cortex and hippocampus.The level of tau phosphorylation at the two sites above were lower in the cortex of 4-month SF mice than those of the control group(p-tau(Ser396)P = 0.016,p-tau(Thr231)P = 0.020).While p-tau(Ser396)was decreased in the hippocampus of 4-month SF mice(P = 0.049),p-tau(Thr231)was not significantly different from the control group(P = 0.33).4.Reactive increase of microglia was observed in the cortex(P =0.044)and hippocampus(P =0.0043)of 1.5-month SF mice,while the increase of microglia in 4-month SF mice was mainly found in the hippocampus.There were no significant differences in GFAP expression between the sleep fragmentation group and the control group of both durations.5.The brain glucose metabolism was increased in 1.5-month SF mice(SUV 1.47 VS SUV 2.12,P =0.015).It did not change significantly in 4-month SF mice compared with the control group(SUV1.48 VS SUV1.59,P =0.51).Conclusions 1.Chronic sleep fragmentation can lead to AD-like pathological changes in the brain of normal mice.2.There are differences in the effects of sleep fragmentation of different durations on AD pathological markers,inflammatory response and glucose metabolism level in mouse brain.Long-term fragmented sleep stimulation may cause adaptive changes in mice.