engleski

Follow up of cognitive deficits and insulin- degrading enzyme expression in a rat model of sporadic Alzheimer's disease

Introduction Growing body of evidence suggests the involvement of insulin degrading enzyme (IDE) in sporadic Alzheimer’s disease (sAD) pathophysiology. IDE degrades also amyloid β (Aβ) peptide, found pathologically accumulated in sAD. Rats treated intracerebroventricularly with streptozotocin (STZ-icv) have been recently proposed as an experimental sAD model. We have done a long-term follow-up of cognitive deficits and hippocampal IDE pathology in STZ-icv rat sAD model. Methods Wistar rats were given STZ-icv (3mg/kg) while controls received vehicle only. Cognitive functions were tested by Morris Water Maze Test (MWM) and Passive Avoidance Test (PA) at different time points (one week to six months following the STZ-icv treatment). IDE protein and mRNA expression was measured in hippocampus (HPC) by SDS-PAGE electrophoresis/immunoblotting and RT- PCR, respectively, and data analysed by Mann- Whitney test (p<0.05). Aβ accumulation was visualised by Congo red staining. Results Learning and memory deficits was found as early as two weeks following the STZ-icv treatment (- 25, 03%), and persisted up to six months after STZ- icv (- 28, 61% MWM ; -94, 36% PA). IDE protein expression was found decreased one month after the STZ-icv administration (-55, 88%), persisting decreased till six months (-26%), while IDE mRNA expression remained unchanged until three months, when it started to decrease (-18, 9%), further deteriorating up to six months after STZ-icv administration (-38, 20%). Aβ accumulation in meningeal capillaries was found not earlier than three months after STZ-icv injection. Conclusion The onset of cognitive deficits in sAD model does not correlate with IDE protein and mRNA changes in HPC which appear later on in the time-course of disease model. The appearance of cerebral amyloid angiopathy seems to correlate with the IDE pathology, being manifested after the cognitive deficits have already been developed. Once developed, IDE and Aβ pathology may contribute to cognitive deficits progression. Acknowledgement: Supported by MZOS and DAAD

Alzheimer's disease; streptozotocin; insulin degrading enzyme; learning and memory

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