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

Autori
Smailović, Una ; Knezović, Ana ; Mandel, Silvia ; Moussa, Youdim ; Šalković-Petrišić, Melita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum biologorum / - Zagreb, 2013, 88-88

Skup
7th Croatian Congress of Pharmacology

Mjesto i datum
Zagreb, Hrvatska, 18.09.2013. - 21.09.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
iron chelator; Alzheimer's disease; streptozotocin

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA