Effect Of Trehalose On Hippocampal Oxidative Stress Injury Induced By Lsoflurane In APP Trangenic Mice

Background: Alzheimer’s disease is one of neurodegenerative diseases. Accompanied by acceleration of the process of aging population, more and more people have suffered from Alzheimer’s disease. China is one of the world’s most populous country, and is of an elderly population that the aging population possess more than 120 million. And the prevalence rate ofdementia is 3~8%, of which more than 60 percent are sick with Alzheimer’s disease.Chinese patients account for a quarter of the number of cases in the world. With the further expansion of China’s aging population, the number of patients will exceed 20 million in the further 60 years. Alzheimer’s disease has bring about heavy mental and economic burden to the patient’s family as well as the society. Alzheimer’s disease is characterized by nerve fiber entanglement, senile plaque in CAⅠof cerebral cortex and hippocampus. The pathogenesis is not very clear, and there is no satisfactory treatment methods or measures. Recently, the relationship between oxidative stress as well as free radical damage and neurodegeneration in Alzheimer’s disease has become a hot research topic. Cumulative oxidative stress probably induce impairment of the DNA repair system, cellular damage, and mitochondrial dysfunction, all of which have been known as key causes in the acceleration of aging process and the development of Alzheimer’s disease. It has been reported that oxidative imbalance as well as resultant neuronal damage may play a main role in the initiation and progression of neurodegenerative diseases. There are 8 million patients with Alzheimer’s disease accepted general anesthesia in the world each year so far. Inhaled anesthetics isoflurane is one of common drugs used in clinical, animal experiment and clinical study have shown that clinical relevant concentration of isoflurane may inhibit cellular autophagy,increaseβ-amyloid accumulation, induce neuronal apoptosis, and aggravate the pathophysiological process of Alzheimer’s disease. But whether its mechanism is correlated with oxidative stress,the exact signaling pathways as well as regulatory mechanism are not fully clear yet, and tobe elaboratedin further study. Trehalose is a natural protective agent. Due to its stability,non-toxic and all natural property, trehalose has become popular in the field of domestic and foreign pharmaceutical studies. Animal experimental study showed that trehalose can improve the performance of AD transgenic mice in behavior test, alleviate the aggregation level of Tau protein and amyloid beta protein in brain, so that exertan anti-oxidation effect.However, whether trehalose can antagonise the neurotoxicity induced by isoflurane is not fully clear. Therefore, it is significant to investigate the protective effect of trehalose as well asthe impact of trehalose on hippocampus oxidative stress damage induced by isoflurane.Purpose: To explore the potential protective effects of trehalose and the impact of isoflurane on hippocampus oxidative stress damage in APP trangenic mouse.Methods: 12-month-old APP transgenic mice were allocated into 4 groups(n=15 each)at random: Group normal control(group Control) were left intact.; Group isoflurane(group Iso) were treated with 1.4% isoflurane 2h; Group isoflurane + trehalose(group Iso+Tre) were treated with trehalose at concentration of 400 μg/kg by intraperitoneal injection 30 min before anesthesia, then treated with 1.4% isoflurane 2h; Group trehalose(group Tre) were treated with trehalose at concentration of 400 μg/kg by intraperitoneal injection.Some of mice were treated with Morris water-maze to investigate learning and memory ability24 hafter anesthesia. Some of mice were killed to separate bilateral hippocampus tissue 6h after anesthesia, one side of hippocampus was prepared to brain tissue homogenate, reactive oxygen species(ROS) level was measured by DCFH-DA fluorescence assayusing excitation and emission wavelengths of 488 and 525 nm, malondialdehyd(MDA) contents and superoxide dismutase(SOD), glutathion peroxidase(GSH-Px) and catalase(CAT) activities were detected using commercial kits. The other side of hippocampus was prepared to cerebral frozen section, hippocampus neuronal apoptosis was observed by TUNEL staining,expression of hippocampu glutathion peroxidase(GSH-Px),catalase(CAT)andsuperoxide dismutase(SOD)were detected by immunohistochemistry.Results: In comparison with group Control, escape latency was significantly increased(P<0.05), spatial exploring time was significantly reduced(P<0.05), hippocampus MDA contents was significantlyincreased(P<0.05), ROS level was significantly increased(P<0.05), SOD、GSH-Px and CAT activities was significantly decreased(P <0.05), and rate of hippocampus neuron apoptosis significantly increased(P <0.05) in group Iso. Compared with group Iso, escape latencywas significantly reduced(P<0.05), spatial exploring time wassignificantly increased(P<0.05), hippocampus ROS level was significantly decreased(P<0.05), MDA contents was significantly decreased(P<0.05), SOD, GSH-Px and CAT activities was significantly increased(P<0.05), and rate of hippocampus neuron apoptosis significantly reduced(P<0.05) in group Iso+Tre.Conclusion: Isoflurane could induce learning and memory impairment of APP trangenic mouse, aggravate hippocampus oxidative stress injury, and trehalose could alleviate neurotoxicity of isoflurane via inhibition of oxidation.