Naslov
Brain insulin and insulin receptor dysfunction triggers Alzheimer-like pathology in an experimental rat model.

Autori
Salkovic-Petrisic, Melita ; Grünblatt, Edna ; Osmanovic, Jelena ; Hoyer, Siegfried ; Riederer, Peter

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

Izvornik
Neurodegenerative Diseases. Suppl 1 / Nitsch Roger M ; Hock C - Basel : Karger Publishers, 2007, 236-236

ISBN
978-38055-8282-7

Skup
8th International Conference AD/PD

Mjesto i datum
Salzburg, Austrija, 14.03.2007. - 18.03.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Alzheimer's Disease; Experimental Model; Streptozotocin; Brain Insulin

Sažetak
Background/aims. Decreased brain glucose/energy metabolism and cognitive deficits similar to those found in sporadic Alzheimer’ s disease (sAD) were reported in streptozotocin (STZ)-intracerebroventricularly (icv) treated rats, suggesting them as an experimental sAD model. Brain insulin receptor (IR) signaling cascade dysfunction found post mortem in sAD, has been reported recently also in STZ-icv rat model, in which brain insulin and IR activity, and tau protein as both a terminal substrate in IR signaling cascade, and a pathological marker of sAD, were here investigated. Methods. Gene expression of insulin and IR, and alterations of IR-beta subunit, protein tyrosine kinase (TK) activity and tau protein were measured by means of quantitative RT-PCR, ELISA, PTK assay and Western blot, respectively, in rat frontoparietal cortex (CTX) and hippocampus (HPC), three months following the STZ-icv (1 mg/kg) treatment. Results. The expression of insulin-1 and -2 mRNA was found significantly decreased in HPC and CTX, respectively. Both regions demonstrated significantly decreased IR mRNA expression. Significantly increased concentration of phosphorylated IR-beta subunit has been found in CTX, with no change in HPC, while significantly increased TK activity was found in HPC only. Total and phosphorylated (GSK-3 related) tau protein was significantly increased in HPC of STZ-icv rats. Conclusion. STZicv-induced discrepancy between reduced IR gene expression and increased phosphorylated IR tyrosine residues/TK activity may indicate imbalance between its phosphorylation/dephosphorylation causing IR dysfunction, and subsequently triggering tau hyperphosphorylation, which points to the brain insulin/IR dysfunction as a possible pathological core in the generation of sAD. Supported by Croatian MZOS and DAAD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA