The Role Of RTN3 In The Pathological Process Of Senile Dementia In The Brain Of Diabetic Rats And Its Mechanism

ObjectiveLaboratory and epidemiological studies have provided direct evidence that diabetes is an independent risk factor which can trigger Alzheimer’s like change in brain and cause cognitive deficits.To detect the possible mechanism underlying diabetes mellitus susceptible developing to Alzheimer’s disease from the perspective of β-amyloid generation and neuronal functions,experiments were designed to detect the possible regulation role of RTN3 because this reticulon family member has been show having effects on β-secretase activity regulation and further reduce amyloid-beta(Aβ)generation.Moreover,studies have demonstrated that over-expressing RTN3 mice showed dystrophic neurites which could be peculiarly stained by antibody to RTN3.So,we want to determine whether RTN3 play a role in diabetes mellitus conditions developing to Alzheimer’s like changes.Research design and methodsDiabetic animal model to mimic human type 2 diabetes mellitus was established based on Sprague dawley rats by chronic high-fat-diet feed combining modest small does streptozotocin induction.Routine methods of Morphological and protein assay were performed to detect target proteins changes.Co-immunoprecipitation was employed to exam protein-protein binding.Water mass test was used to study the change of cognitive function.ResultsPresent results revealed that monomeric RTN3 was decreased in diabetic brain,meanwhile its aggregated form HW-RTN3 increased correspondingly,which was related with dystrophic neurites and impaired neuronal functions.Simultaneously,binding of monomeric RTN3 and BACE1 was decreased in diabetic brain.Thereby reduced inhibition of RTN3 on the activity of BACE1 and resulted in increased formation of amyloid beta in diabetic brain.Moreover,diabetic rats showed reduction in cognitive function.Conclusion:RTN3 could influence Alzheimer’s like pathological changes in diabetic brains from two aspects:reduced interaction between monomeric RTN3 and BACE1 is related with active Aβ generation in brain of diabetes mellitus as mono-RTN3 has function in inhibiting β-secretase cleavage activity on APP.Meanwhile increased aggregated form RTN3 impairs neuronal structure and biological function and further result in neurodegenerative pathology.