Naslov
The origin of sporadic alzheimer disease – Is it brain insulin resistant state?

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

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

Skup
The third Croatian Neuroscience Meeting

Mjesto i datum
Zadar, Hrvatska, 24.09.2009. - 28.09.2009

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
Sporadic Alzheimer disease; insulin receptor; streptozotocin; amyloid beta

Sažetak
Background. Sporadic Alzheimer disease (sAD) is associated with brain insulin receptor (IR) signalling abnormalities whose ethiopathogenesis is unclear in the course of sAD. Rats that have been intracerebroventricularly treated with streptozotocin (STZ-icv), a drug selectively toxic for insulin producing/secreting cells and IR, have been recognized recently as the non-transgenic, experimental sAD model, suitable for brain IR signalling cascade exploration. Aim. We investigated the time course of brain IR signalling dysfunction in relation to amyloid pathology development in STZ-icv rat model of sAD. Methods. RT-PCR and immunoblotting were used for hippocampal IR signalling cascade gene and protein expression measurements, respectively and data were analyzed by Cruscal-Wallis ANOVA median/Mann- Whitney U test. Amyloid β (Aβ) aggregation was detected by Congo red staining and immunohistochemistry. Results. Our results demonstrated alterations in brain IR signalling cascade starting from the decreased insulin gene expression, followed by a decreased expression of IR mRNA and protein, found as early as 1 month following the induction of sAD-like condition and persisting up to 9 months afterwards. Downstream dysfunction of IR signalling pathway manifested as decreased ratio of phosphorylated/non-phosphorylated glycogen synthase kinase-3 was found not earlier than 3 months after STZ-icv treatment and was followed by tau protein hyperphosphorylation, cerebral amyloid angiopathy, intraneuronal Aβ aggregation and plaque-like formation (not earlier than 6 months after the STZ-icv treatment). No change in amyloid precursor protein gene expression was found while the expression of insulin degrading enzyme gene/protein was decreased. Conclusion. Based on this experimental approach, sAD could be considered as an insulin resistant brain state which precedes and eventually triggers Aβ pathology.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA