engleski

Therapeutic effects of multifunctional iron-chelating agent in a streptozotocin-induced rat model of sporadic Alzheimer's disease

Introduction: Rats treated intracerebroventricularly with streptozotocin (STZ-icv) have recently been proposed as a nontransgenic model of sporadic Alzheimer’s disease (sAD). We aimed to assess the therapeutic potential of a novel multifunctional iron-chelating compound M30 in STZ-icv rat model. Materials and methods: Adult male Wistar rats were injected icv with STZ (3 mg/kg) or vehicle (control) and sacrificed 2 and 4 weeks after the treatment. Half of the STZ-icv treated rats was subjected to M30 oral treatment (10 mg/kg 3x a week) initiated 10 days after the STZ treatment. Protein expression of insulin receptor (IR), insulin degrading enzyme (IDE), phospho and total glycogen synthase kinase-3β (GSK3β) and phospho tau in hippocampus was measured by SDS-PAGE and immunoblotting. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results: M30 treatment significantly increased the p/tGSK3β ratio in STZ-icv treated rats compared to the STZicv (+52%) and control (+100%) treatment after 4 weeks, respectively. STZ-icv treatment significantly increased (+35% to +44%) the expression of p-tau compared to the control at both time-points while additional M30 treatment significantly reduced it to the control values after 2 weeks. After 4 weeks IDE expression was significantly decreased in STZ-icv treated rats regardless the M30 treatment (-36%) while IR expression was significantly decreased in M30-treated STZ-icv rats (-24%) compared to the controls. Conclusion: M30 treatment demonstrates therapeutic potential in STZ-icv model of sAD by reducing the activity of GSK3β and consequent tau protein hyperphosphorylation in the hippocampus. Supported by MZOŠ and Verein zur Durchfuhrung Neurowissenschaftlicher Tagungen e.V.

iron chelator; Alzheimer's disease; streptozotocin

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