Naslov
Brain insulin dysfunction triggers plaques formation in rat model of sporadic alzheimer's disease

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

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

Izvornik
Alzheimer's & Dementia / Khachaturian, Zaven - Washington (MD) : Elsevier, 2008, P1-003

Skup
Alzheimer's Association International Conference on Alzheimer's disease

Mjesto i datum
Chicago (IL), Sjedinjene Američke Države, 26.07.2008. - 31.07.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Alzheimer's disease; streptozotocin; insulin; plaque

Sažetak
Background. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats have been proposed as the experimental model of sporadic Alzheimer&#8217; s disease (sAD) which contrary to the transgenic mice models is not related to gene manipulations. STZ is a cytotoxic drug capable of inducing damage to insulin producing/secreting cells and to insulin receptor (IR) as well. Preliminary data suggested time-dependent changes of brain IR signalling cascade dysfunction resulting in tau hyperphosphorylation, and congophylic amyloid angiopathy which could not have been seen before 3 months after STZ-icv treatment. Objective. We investigated whether damage to brain insulin/IR system in long-term could trigger A&#946; pathology in STZ-icv experimental model of sAD . Methods. Gene expression of insulin I/II (Ins-I and Ins-II), insulin receptor (IR) and insulin degrading enzyme (IDE) was measured by RT-PCR, while IR and IDE protein expression was measured by immunoblotting in hippocampus of STZ-icv treated (3 mg/kg) male Wistar rats, three and six months following the treatment. A&#946; expression was visualized by immunohystochemistry (A&#946; 1-42) and Congo red staining. Cognitive deficits were measured by Morris Water Maze Test. Data were analyzed by Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05). Results. STZ-icv treated rats demonstrated cognitive deficits both after 3 and 6 months following the STZ treatment. Decreased expression of Ins-I gene (85% and 57%) and of both IR mRNA (19% and 26%) and protein (23% and 28%) were found 3 and 6 months after STZ-icv treatment as well as decreased expression of both IDE mRNA (19% and 38%) and protein (22% and 21%). These neurochemical changes were accompanied by A&#946; 1-42 intracellular tissue aggregates after 3 months and formation of primitive congophyllic amyloid plaques after 6 months found in temporo-parietal cortex and hippocampus of STZ-icv treated rats. Conclusion. Brain insulin and IR signaling cascade dysfunction precedes and induces time-dependent A&#946; plaque development in experimental sAD. Considering the similarities between the human sAD and STZ-icv rat model in cognitive deficits, decreased brain glucose/energy metabolism, oxidative stress and brain IR signalling dysfunction, it seems likely that insulin resistant brain state could precede and trigger A&#946; pathology and plaque formation in human sAD as well. Supported by MZOS (108-1080003-0020) and DAAD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA