Brain insulin dysfunction triggers plaques formation in rat model of sporadic alzheimer's disease (CROSBI ID 551232)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Šalković-Petrišić, Melita ; Osmanović, Jelena ; Grünblat, Edna ; Siegfried, Hoyer ; Riederer, Petr
engleski
Brain insulin dysfunction triggers plaques formation in rat model of sporadic alzheimer's disease
Background. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats have been proposed as the experimental model of sporadic Alzheimer’ 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 Aβ 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. Aβ expression was visualized by immunohystochemistry (Aβ 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 Aβ 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 Aβ 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 Aβ pathology and plaque formation in human sAD as well. Supported by MZOS (108-1080003-0020) and DAAD.
Alzheimer's disease; streptozotocin; insulin; plaque
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Podaci o prilogu
P1-003-p1-003.
2008.
objavljeno
Podaci o matičnoj publikaciji
Alzheimer's & Dementia
Khachaturian, Zaven
Washington (MD): Elsevier
Podaci o skupu
Alzheimer's Association International Conference on Alzheimer's disease
poster
26.07.2008-31.07.2008
Chicago (IL), Sjedinjene Američke Države