Naslov
Insulin resistant brain state triggers sporadic alzheimer disease: experimental approach

Autori
Šalković-Petrišić, Melita ; Osmanović, Jelena ; Grünblat, Edna ; Hoyer, Siegfried ; Riederer, Peter

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

Skup
6th International Congress on Vascular Dementia

Mjesto i datum
Barcelona, Španjolska, 19.11.2009. - 22.11.2009

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Insulin receptor; sporadic alzheimer disease; amyloid beta; tau protein; streptozotocin

Sažetak
Background. Impaired signalling of brain insulin receptor (IR) is involved in cognitive decline, as well as in decrement of glucose utilization and energy metabolism, and in metabolism of amyloid beta (Aβ) and tau protein. A growing body of evidence points to the dysfunction of brain IR signalling in sporadic AD (sAD), suggesting that it is a consequence of amyloid (Aβ) pathology. Aim. We explored whether damage of the brain insulin/IR signaling pathway could trigger Aβ pathology in rat sAD model produced by intracerebroventricular application of streptozotocin (STZ-icv), drug selectively toxic for insulin producing/secreting cells and IR. Methods. Gene and protein expression was measured by RT-PCR and immunoblotting/ELISA, respectively, in hippocampus of STZ-icv rat model. Aβ expression was visualized by immunohystochemistry (Aβ1-42) and Congo red staining. Data were analyzed by Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05). Results. Decreased expression of insulin gene and IR mRNA and protein was found 1 month after STZ- icv treatment while downstream the IR signaling pathway, decreased ratio of phosphorylated/non- phosphorylated glycogen synthase kinase-3, and tau protein hyperphosphorylation were found 3 months after STZ-icv treatment. Cerebral amiloid angioapthy and Aβ1-42 intraneuronal tissue aggregates were found not earlier than 3, and amyloid plaque-like formations not earlier than 6 months after STZ-icv treatment. APP gene expression was unchanged while expression of IDE mRNA/protein was decreased. Conclusion. Insulin resistant brain state precedes and eventually triggers Aβ pathology in non- transgenic, STZ-icv rat model of sAD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA