Effect Of 9-month-old AD Brain Glucose Metabolism In Mice With Curcumin

ObjectiveAlzheimer’s disease (AD) is clinically characterized with the memory loss, cognitive function impairment together with degradation of language, visual and motor coordination ability, eventually dying of the serious complications such as infection. Current diagnosis depends mostly on Psychiatric Rating Scale on the onset of symptoms. Progressive mental deterioration occurs after the clinical symptoms. The existing treatments are difficult to obtain satisfactory curative effect. So the early diagnosis and intervention are essential to treatment of AD.The main pathological changes of AD include senile plaques(SPs), neurofibrillary tangles (NFTs), neuron loss, etc.While95%of AD are sporadic AD (SAD), and SAD is a disease closely related to the age.The interaction of genetic, environmental and metabolic factors contribute to the initiation of SAD.Therefore, AD brain blood supply,glucose uptake and metabolism impairment is the cause of neurodegenerative rather than the result.Based on the research about effect of curcumin on6months APPswe/PS1dE9double transgenic mice cerebral metabolism, the present study was designed to observe the effect of Curcumin on9months mice cerebral metabolism.The study made use of Micro-PET to get data and information of cerebral energy metabolism, immunohistochemical and Western blot to observe the expression of Glucose transporter1(GLUT1), Glucose transporter3(GLUT3)and insulin receptor substrate2(IRS2).By these, to study that curcumin improves for9months APPswe/PS1dE9double transgenic mouse metabolism, in order to further explore mechanism of neuroprotective effect of curcumin in different ages.Material and Methods1. APP/PS1double transgenic mice (AD mice) of3months were randomized into APP/PS1dtg, Rosiglitazone (RSG) group and curcumin-treated groups of high, medium and low doses. Genetic background and age-matched C57/BL6J mice were used as normal control group. Mice were treated through intragastric administration once daily for6months.2. The spatial learning and memory together with memory retention ability were assessed by Morris water maze to evaluate the therapeutic effects of curcumin on cognitive function.3. Cerebral glucose metabolism was detected using functional imaging technique-Micro-PET to address the effect of curcumin on cerebral energy metabolism of AD mice. 4. The expression of GLUT1、GLUT3and IRS2in the hippocampus of AD mice was examined using immunohistochemistry and Western blot methods to evaluate the therapeutic effects of curcumin on the expression of cerebral energy metabolism-related proteins.5. Statistical analysis:Data are presented as means±SD. Differences among groups were determined by one-way ANOVA. Differences were considered significant at P<0.05.Results1. The effects of curcumin on ethology, spacial learning and memory ability of AD miceIn Morris water maze test, after curcumin intervention for6months swimming time of groups mice with the increase of training number are declining, although there is a small float. Escape latency period of APP/PS1dtg mice were significantly increased compared with the normal control mice (P<0.05or P<0.01).Compared with APP/PS1dtg mice, the escape latency period of the intervention groups were significantly shortened (P<0.05). The result of the mice swimming distance corresponded to the result of escape latency.2. The effects of curcumin on cerebral glucose metabolism of AD mice using Micro-PET techniqueMicro-PET imaging showed that the average radioactivity of18F-FDG of APP/PS1+RSG group and APP/PS1+curcumin-M were higher than APP/PS1dtg group, APP/PS1+curcumin-H and APP/PS1+curcumin-L groups showed no statistical significance.The average uptake rate of cerebral18F-FDG of APP/PS1+curcumin-M group and APP/PS1+RSG group were higher than APP/PS1dtg group and CON group.3. Effects of curcumin on the expression of GLUT1in the hippocampus of AD mice Immunohistochemistry Results:Compared with CON group mice, GLUT1positive cells of hippocampus CA1area of AD mice were markedly decreased (P<0.01). Compared with APP/PS1dtg group mice, GLUT1positive cells of hippocampus CA1area of APP/PS1+RSG and APP/PS1+curcumin-M were markedly increased(P<0.01), APP/PS1+curcumin-H and APP/PS1+curcumin-L group mice were significantly increased (P<0.05).The results of Western blot:The results of the expression of GLUT1corresponded to the above results.4. The effects of curcumin on the expression of GLUT3in the hippocampus of AD mice Immunohistochemistry Results:Compared with CON group mice, GLUT3positive cells of hippocampus CAl area of AD mice were markedly decreased (P<0.01). Compared with APP/PS1dtg group mice, GLUT3positive cells of hippocampus CAl area of APP/PSl+RSG, APP/PSl+curcumin-H and APP/PSl+curcumin-M group mice were significantly increased (P<0.05), APP/PS1+curcumin-L groups showed no statistical significance.The results of Western blot:The result of the expression of each protein corresponded to the above results.5. The effects of curcumin on the expression of IRS2in the hippocampus of AD mice Immunohistochemistry Results:Compared with CON group mice, IRS2positive cells of hippocampus CA1area of AD mice were markedly decreased (P<0.01). Compared with APP/PS1dtg group mice, IRS2positive cells of hippocampus CAl area of APP/PS1+RSG, APP/PS1+curcumin-H and APP/PS1+curcumin-M mice were significantly increased(P<0.05), APP/PS1+curcumin-L groups showed no statistical significance.Western blot Results:The result of the expression of each protein corresponded to the above results.ConclusionAs the disease progresses, the potential neuroprotective role of curcumin is accomplished by improving cerebral glucose metabolism and affecting the hippocampal expression of energy metabolism-related proteins GLUT1,3and IRS2.