Effects Of Chronic Sleep Deprivation On The Cognitive Function In Mice And The Expression Of β-amyloid As Well As Metabolism-associated Molecules

Objective: This experiment studied the effects of chronic sleep deprivation on the cognitive function in mice, as well as the expression of β-amyloid and metabolism-associated molecules BACE1 and RAGE, thus providing theoretical foundation for preventing the genesis of Alzheimer’s disease(AD) and postponing disease progression.Methods: Divided the 30 healthy male Kunming mice randomly into 3 groups, which were the sleep deprivation group(SD group, n=10), the tank control group(TC group, n=10), and the blank control group(BC group, n=10).(1) Adopted the modified multiple platform method(MMPM) to construct sleep deprivation mice models.(2) Evaluated the cognitive ability of mice through object recognition test(ORT).(3) Observed the morphological changes of nerve cells in prefrontal cortex and hippocampus by HE staining.(4) Observed the ultrastructural changes of the hippocampus and the prefrontal cortical tissue via transmission electron microscopy.(5) Detected the expression of Aβ1-42, β-site amyloid precursor protein cleavage enzyme-1(BACE-1), as well as the receptor for advanced glycation end-product(RAGE) protein in prefrontal cortex and the CA1 region of the hippocampus through immunohistochemistry.Results: 1. Neurobehavioral test results: the exploration time by mices in each group showed no remarkable difference during the mastery stage(P>0.05); while in the recognition stage, the exploration time of new objects by mices in the SD group was notably less than that in the BC and the TC groups(P<0.05); and there was no significant difference between the BC group and the TC group(P>0.05).2. HE staining results: the morphology of nerve cells in the prefrontal cortex and hippocampus in the SD group showed looser arrangement, with ill-defined margins, broadening space, cell body atrophy as well as severe damage relative to the BC and the TC groups. The neurons in the BC and the TC groups displayed regular morphology, with regular cellular arrangement.3. Observation results of the nerve cell ultrastructure in the hippocampus and the prefrontal cortex: the hippocampus and the prefrontal cortex in the SD group presented broadening synaptic cleft, reduced synaptic vesicles, endoplasmic reticulum expansion, markedly reduced mitochondrial quantity, irregular morphology and vacuole-like nucleoplasm; while the neurons in the BC and the TC group had distinct nuclear membrane, mitochondria with structural integrity, and intact Golgi apparatus as well as endoplasmic reticulum.4. Results of immunohistochemistry for detecting the expression of Aβ1-42 protein: the positive expression cells, which were claybank, located in the cytoplasm; when compared with the BC group and the TC group, the expression of Aβ1-42 protein in the prefrontal cortex and the CA1 region of hippocampus remarkably increased(P<0.05) in mices in the SD group, while the expression of positive cells in the BC group and the TC group was less, but there was no distinct difference between the two groups(P>0.05).5. Results of immunohistochemistry for detecting the expression of BACE1 protein: the positive expression cells, which were dark violet, located in the cytomembrane and the cytoplasm; when compared with the BC group and the TC group, the expression in the prefrontal cortex and the CA1 region of hippocampus outstandingly increased(P<0.05) in mices in the SD group, while the expression of positive cells in the BC group and the TC group was less, but there was no distinct difference between the two groups(P>0.05).6. Results of immunohistochemistry for detecting the expression of RAGE protein: the positive expression cells, which were claybank, mostly located in the nuclei and the cytoplasm; when compared with the BC group and the TC group, the positiveexpression of neuron RAGE protein in the prefrontal cortex and the CA1 region of hippocampus markedly increased(P<0.05) in mices in the SD group, while the expression of positive cells in the BC group and the TC group was less, but there was no distinct difference between the two groups(P>0.05).Conclusion:1. Cognitive impairment in mice could be induced by chronic sleep deprivation.2. Morphological and ultrastructural changes of neurons in mice prefrontal cortex and hippocampus might be resulted from chronic sleep deprivation.3. Deposition of Aβ1-42 protein in mice prefrontal cortex and hippocampus might be increased by chronic sleep deprivation.4. Expression of β-site amyloid precursor protein cleavage enzyme-1(BACE-1) and receptor for advanced glycation end-products(RAGE) in mice prefrontal cortex and the hippocampus might be increased by sleep deprivation, which affected the production and transfer of Aβ1-42 protein, resulting in the neurobehavioral changes in mice.