PET/CT Imaging In Diabetic Encephalopathy And The Correlation With IGF1R

As is well known, PET/CT has an important Clinical significance and value todiagnosis, decisions of treatment and efficacy evaluation for patient in a variety ofcentral nervous system diseases, such as epilepsy, senile dementia, Parkinson's disease.Neuroimaging could link changes in the structure of the brain with changes incognitive function. Brain scanning in real time on the brains of Patient with diabetesgiven in three-dimensional imaging of the amount of monitoring, which evaluates theneuroanatomical regions involved in the brains of patients with diabetes, it isimpossible in neuropathology research organizations.Here, brain glucose metabolism levels in Diabetic encephalopathy rat modelwere detected with PET/CT. It is exerted and measured that related pathologicstructural changes and some major functional molecules expression in hippocampus.The results show that the abnormal expression increase of IGF1R or related pathwaysactivation is very related to the occurrence of diabetic encephalopathy. This issupported by the observation that the production of reactive oxygen species is reducedin brains of IGF1R knock-out mice compared with their WT counterparts followingMPTP treatment known to induce a Parkinson's disease-like phenotype. On the otherside, an alternative model suggests that increased neuronal resilience associated withreduced IGF signaling is promoted by enhanced DNA repair capabilities. It isreasonable to speculate that the histone deacetylase SIRT1, an aging regulator thatplays roles in the maintenance of genomic stability may also be a mediator foranti-apoptosis of the reduced IGF signaling protective effect in Alzheimer's disease.In view of the importance of IGF1R knock-out to nerve cells, we inhibited ofIGF1R expression in PC12cells, and reduced the activating level of IGF1R pathwayusing the lentiviral packaging, picked stable transfected cells, namely ΔIGF1R-ofPC12cells. In the follow parts, to investigate underlying details in that IGF1R defectsaffecting the nerve cells consumption and glucose uptake, and take particular attentionto the effects and the interactions between IGF1R, IR, phosphorylation of Aktsignaling pathway.The content of the issue is divided into three parts, the use of imaging, pathology,molecular biology, cell biology techniques,on individual, cell and molecular levels, we studied the important role of IGF1R to the development of diabeticencephalopathy, revealed the interaction between IGF1R signaling pathwaydiminishing, glucose metabolism and IR signaling pathway in nerve cells. Followingthis three-part research brief summary, as follows:1. PET/CT Imaging and Immunohistochemical on DiabeticEncephalopathy in RatsIn this part, first of all, we have established a rat model of diabetes screening bybehavioral experiments, rats suffering from diabetic encephalopathy, and then detectthe level of rat brain glucose metabolism using PE/CT, the final study brainthepathological features of the hippocampus and IR, IGF1R and Glut4in tissue withpathological staining and immunohistochemical methods. The results show that,compared with the normal control group and diabetic group, the level of brain glucosemetabolism in diabetic encephalopathy rats significantly reduced amyloid calm,organization and the cytoplasm have a red dye, the nerve fiber thickening,swellingderangement and so on, like neuropathological characteristics; IR expressionlevel is basically the same among the experimental group, diabetic encephalopathyrats IGF1R expression increased Glut4but the phenomenon of decline, it isnoteworthy that relative to the normal control group, only sufferinghippocampus ofrats with diabetes without suffering from encephalopathy IGF1R expression levelswere significantly reduced.2. IGF1R knock-out PC12cell obtaining and screeningIn accordance with the findings of the first part, only those with diabetes withoutencephalopathy rat hippocampal IGF1R expression levels appear significantlyreduced brain glucose metabolism capacity remained at a high level. Therefore,lentiviral packaging transfection techniques has been used to inhibit IGF1Rexpression in glioma cells PC12, which provided an important model for furtherresearch. After a large number of molecular biology vector assembling and screening,we obtained the IGF1R low expression of the stable transfected celllines-ΔIGF1R-PC12ultimately.3. Study on the Inhibiting IGF1R affected PC12cell glucose metabolismand signal pathwaysThe part of the research,at the cellular level, concerning to the IGF1R defectsacted in cell glucose metabolism and Akt signaling pathway, the major resultwas the IGF1R defects enhanced PC12cells glucose consumption, but still not completelyreversed damage triggered by Aβ25-35in cells; IGF1R defect could promote glucoseuptake in insulin-stimulated PC12cells inthe dose and time manner; IGF1R defectcould improve insulin sensitivity to IR and IRS phosphorylation in PC12cells;extremely important to this study, in ΔIGF1R-of PC12cells, IR showed only need thesense insulin concentration of1/100(0.1nM) of normal PC12cells; in IGF1Rknock-out PC12cells, when Aktphosphorylation pathway was activated, the insulinsensitivity of IR would be improved significantly.This study revealed that IGF1R signaling pathway's role in diabeticencephalopathy, opened up a new direction for related research in nervous systemdiseases, but also provided a new idea for the treatment of diabetic encephalopathy,relevant drug development and target sites.