engleski

Therapeutic potential of multifunctional iron-chelating agent M30 in a rat model of sporadic Alzheimer's disease

Introduction: Central administration of streptozotocin (STZ-icv) is shown to induce Alzheimer-like changes due to the STZ-icv rat model has been proposed as an animal model of sporadic Alzheimer’s disease (sAD). We aimed to assess the therapeutic potential of a novel multifunctional iron-chelating compound M30 in a STZ-icv rat model. Materials and methods: Adult male Wistar rats were injected icv with STZ (3 mg/kg) or vehicle (control). STZ-icv injected rats were treated orally with water (STZ) or M30 (10 mg/kg 3x a week) starting 8 days after icv treatment (STZ+M30) and sacrificed 2 weeks after icv treatment. Protein expression of phospho (p)-tau protein PHF13 and AT8, phospho and total glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5) in hippocampus was measured by SDS-PAGE. Brain iron levels were detected by Prussian blue iron staining. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results: M30 treatment decreased STZ-icv-induced increment in p-tau PHF13 expression (p<0.05), compared to STZ-icv treatment alone. AT8 expression and GSK3β activity remained unchanged in all groups. CDK5 expression was found significantly decreased both in STZ and STZ+M30 compared to the control (p<0.05). M30 treatment reduced positive signal of pathological iron accumulation in the STZ-icv rat brain. Conclusion: M30 treatment demonstrates therapeutic potential in STZ-icv model of sAD and further supports the neuroprotective role of multifunctional iron-chelator M30 providing evidence on the molecular mechanisms of the therapeutic potential of M30 in STZ-icv model of sAD. Supported by MZOS and Verein zur Durchfuhrung Neurowissenschaftlicher Tagungen e.V.

iron-chelator M30; streptozotocin; Alzheimer; tau

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