engleski

The onset of brain insulin dysfunction following the streptozotocin central application in rat

Introduction: A growing body of evidence indicates that impairments in brain insulin signalling have important role in early sporadic Alzheimer’s disease (sAD) but their onset in relation to the cognitive impairment has not been clarified. Recently, brain insulin dysfunction was found also in streptozotocin (STZ)-intracerebroventricularly (icv) treated rats, which represent experimental model of sAD, suitable for determining this neurochemical - cognitive impairment causal relationship. Materials and methods: Male Wistar rats (three months old) were injected with STZ (3mg/kg) bilaterally into the lateral ventricles. Control animals were injected icv with vehicle only. Cognitive functions were tested by Morris Water Maze Swimming Test before sacrifice, two weeks and one month following the STZ-icv treatment, respectively. Protein expression of insulin receptor (IR), insulin-degrading enzyme (IDE) and protein kinase B (Akt/PKB) in hippocampus (HPC) was measured by SDS-PAGE electrophoresis, followed by Western blot analysis. Data were analysed by Mann-Whitney U test (p<0.05). Results: Deficit in learning and memory, found two weeks following the STZ-icv treatment (-33%) in comparison to the controls, demonstrated further deterioration as measured 1 month following the STZ-icv application (-54%). However, in spite of that, no change in protein expression of IR, Akt/PKB and IDE in HPC could have been observed two weeks following the STZ-icv application, in comparison to the control rats, while significantly decreased expression of IR (- 19.5%) and IDE (-55%) was found after one month. Akt/PKB protein expression remained unchanged. Conclusion: Results suggest that in respect to the hippocampal protein expression of IR, Akt/PKB and IDE, STZ-icv induced deficit in learning and memory seems to appear earlier than neurochemical manifestation of brain insulin system dysfunction in rats. Acknowledgement: Supported by MZOŠ (108- 1080003-0020) and DAAD projects.

insulin receptor; streptozotocin; cognition; Alzheimer's disease

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