engleski

Acute changes of brain insulin dysfunction in mouse model of sporadic Alzheimer’s disease

Introduction: Recent studies of early changes in sporadic Alzheimer’s disease (sAD) suggest that brain insulin system dysfunction has important role in the onset of the disease. Streptozotocin (STZ) given intracerebroventricularly (icv) as an experimental model induces also the sAD like insulin system alterations. The acute neurochemical impairment of STZ-icv treatment is not investigated thoroughly to represent suitable sAD model. Materials and methods: Female mice (strain C57Bl/6, four months old) were injected icv with STZ (1mg/kg). Control animals were injected vehicle only. The animals were sacrificed one hour following the STZ-icv treatment. Protein expression of insulin receptor (IR), phosphorylated glycogen synthase kinase 3β (pGSK3β), total GSK3, phosphorylated tau protein (pSer396, PHF13) and phosphorylated tau protein (pSer202/Thr205, AT8) in hippocampus (HPC) and parietal cortex (PC) was measured by SDS-PAGE electrophoresis, followed by Western blot analysis. Data were analysed by Mann-Whitney U test (p<0.05). Results: One hour after the injection only the expression of PHF13 was found significantly increased (+26%) in HPC in comparison to the control. In addition to the increased expression of PHF13 (+37%), the expression of AT8 was found increased (+96%) in PC. The protein expression of IR and phospho/total GSK3β was found significantly decreased in PC, -20% and -19%, respectively. Conclusion: Results suggest that acute changes in PC seem to appear earlier and were more pronounced than in HPC. Alterations found in PC conforms the STZ effect on brain insulin system, while increased expression of AT8 may indicate the acute reaction to the procedure itself.

insulin signalling; Alzheimer's disease; streptozotocin

nije evidentirano