Naslov
Altered expression of insulin receptor in hippocampus of streptozotocin intracerebroventricullary treated rats

Autori
Osmanović, Jelena ; Šalković-Petrišić, Melita ; Riederer, Peter

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

Izvornik
Abstracts of the 5th Croatian Congress of Pharmacology and 2nd Congress of Croatian Physiological Society ; u: Periodicum Biologorum. Supplement / Vitale, Branko - Zagreb : Hrvatsko prirodoslovno društvo, 2007, 109-109

Skup
Croatian Congress of Pharmacology (5 ; 2007) ; Congress of Croatian Physiological Society (2 ; 2007)

Mjesto i datum
Osijek, Hrvatska, 19.09.2007. - 22.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
insulin receptor; hippocampus; streptozotcin; Alzheimer's disease

Sažetak
Ethiopathogenesis of sporadic Alzheimer disease (SAD) is associated whit changes in brain glucose metabolism particularly in the brain regions connected with cognition and memory. Glucose metabolism in the brain is partly controlled by insulin in the brain which binds to the neuronal insulin receptor (IR) demonstrating signal transduction mechanism similar to the one at the periphery. Following insulin binding, IR becomes autophosphorylated and binds insulin receptor substrate which transduces the signal downstream the phosphatidylinositol-3 kinase pathway inactivating glycogen synthase kinase (GSK-3). GSK-3α isoform is involved in the regulation of metabolism of amyloid-β peptides and GSK-3β isoform is involved in tau-protein phosphorylation. Therefore, changes in the phosphorylation/dephosphorylation homeostasis of IR signal cascade are capable of causing alterations in amyloid precursor protein metabolism and tau hyperphosphorylation, both known as the major hallmarks of SAD. In the human post mortem brain tissue of SAD patients IR density was found increased while IR mRNA and protein expression as well as IR tyrosine kinase were found decreased. Brain insulin system has also been investigated in experimental AD model, rats treated intracerebroventricularly (icv) with a betacytotoxic drug streptozotocin (STZ). STZ-icv rat model demonstrates brain glucose metabolism changes and deficit in learning and memory that resemble those found in AD patients. We have recently reported altered expression of enzymes downstream the IR signaling pathway ; decreased phosphorylated GSK-3/non-phosphorylated GSK-3 (p-GSK-3/ GSK-3) ratio and increased level of p-tau protein in the hippocampus of STZ-icv treated rats, three months following the drug (1 mg/kg) icv treatment. In these rats increased expression of IR protein was found in hippocampus. We were investigated the changes of IR protein expression in the hippocampus of rats treated with a higher STZ-icv dose three month after the drug icv treatment. Three-month-old male Wistar rats (Department of Pharmacology, School of Medicine, University of Zagreb) were given general anaesthesia (chloralhydrate 300 mg/kg, ip), followed by STZ (3 mg/kg), dissolved in 0.05M citrate buffer pH 4.5 injection bilaterally into the lateral ventricle (2  L/ventricle). Control animals were given vehicle icv. Cognitive functions were tested by Morrris Water Maze Swimming Test. Animals were sacrificed three months after the drug treatment. IR protein expression was measured by SDS electrophoresis followed by a Western blot analysis. Data were analysed by Mann-Whitney U test (p<0.05). Cognitive deficits in learning and memory were found 3 months following the STZ-icv treatment (p<0.05). These cognitive deficits were followed by decreased levels (-23%) of IR found in hippocampus of STZ-icv treated rats in comparison to the control ones (135.67± ; 5.4 vs. 175.33± ; 5.5) (p<0.05). Decreased IR expression in hippocampus of rats treated with a higher STZ-icv dose is in line with SAD human data suggesting that STZ-icv treated rats are useful tool in modelling of SAD. Acknowledgement: Suported by DAAD and Croatian MZOS (108-1080003-0020).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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