Long-term Sleep Restriction Result In Functional Changes Of Microglia And Cognitive Impairment Of Adolescent Mice

Adequate sleep is very important to maintain the normal operation of the body’s physical and psychological activities.Due to the accelerated pace of society and the increased work pressure,more and more people are suffering from different degrees of sleep restriction which seriously affect peoples’ normal life.At present,the research of the mechanism of sleep restriction mainly focus on the study of functions of neurons in the brain,but the research on microglia is less.In recent years,depending on the development of the biological research technique,the functions of microglia,the immune cell of central nervous system,are being gradually recognized in sleep.But its role in the physiological function and pathological changes of sleep is not clear.As a steady state maintainer of the central nervous system,microglia have different activation phenotypes and perform different functions on neurons under different activation states.By establishing an animal model of adolescent sleep restriction and combined with the synaptic pruning functions of microglia,this research reveals the cell regulation mechanism of synaptic plasticity in hippocampal neurons.On this basis,a preventive measure of cognitive impairment caused by potential sleep deprivation is proposed.In this experiment,the adolescent sleep-restricted mice are used as the experimental model and divided into three groups: Control group(Control,Con),Sleep restriction group(SR),and Minocycline group(SR+Mino).The sleep limit time are 6h/d for 7 consecutive days,and mice are intraperitoneally injected with minocycline(20 mg/kg).Behavioral test(cognitive function: object spatial positioning test OLT,object discrimination test NORT,novelty inhibition feeding test NSFT,open field test),cell level test(microglia morphology change and protein molecule colocalization: Immunofluorescence Staining method),molecular level test(Qt-PCR and Western blot)are used to detect the effect of sleep restriction on the brain of adolescent mice.The results show that the sleep restriction leads to cognitive impairment,and morphology of microglia is changed,with the increased expression of phagocytosis-related molecules(TREM2,CD68).It can be proved that microglia exhibit enhanced activation of phagocytic capacity.The protein level of PSD95 is found decreasing through Western blot detection and the phagocytic capacity of microglia to PSD95 is found increasing through immunofluorescence co-localization technique,and the neuronal activity is abnormal.This illustate that the synaptic pruning functions of microglia is enhanced after adolescent mice suffering from sleep restriction and the neuronal activity is affected and function is abnormal.In addition,the minocycline can inhibit the activation state of microglia,reduce the loss of neurons PSD95,and improve abnormal behavior.In summary,sleep restriction of adolescent mice can activate microglia to produce a stress response about synaptic pruning ability and results in abnormal neuronal activity,and the cognitive function of mice is impaired.Inhibition of microglial activation can partially improve the abnormal behavior of adolescent mice caused by long-term sleep restriction.This provides scientific research reference and guidance for the prevention and treatment of abnormal behavior in adolescents caused by long-term sleep restriction.