Pregled bibliografske jedinice broj: 408280
Glucose Transporter Type 2 - Does It Pave the Way to Sporadic Alzheimer's Disease?
Glucose Transporter Type 2 - Does It Pave the Way to Sporadic Alzheimer's Disease? // Book of Abstracts
Nürnberg, Njemačka, 2008. (pozvano predavanje, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 408280 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Glucose Transporter Type 2 - Does It Pave the Way to Sporadic Alzheimer's Disease?
Autori
Salkovic-Petrisic, Melita ; Grünblatt, Edna ; Osmanovic, Jelena ; Hoyer, Siegfried ; Riederer, Peter
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
Book of Abstracts
/ - , 2008
Skup
Ehrlich II: Magic bullet Conference on the occasion of the 100th Anniversary of the Nobel Prize awarded to Paul Ehrlich
Mjesto i datum
Nürnberg, Njemačka, 03.10.2008. - 05.10.2008
Vrsta sudjelovanja
Pozvano predavanje
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
sporadic Alzheimer disease; insulin receptor; brain; GLUT-2; amyloid beta
Sažetak
Background: Sporadic type of Alzheimer’ s disease (sAD) is associated with brain insulin receptor (IR) signalling abnormalities. The sequence of these events in relation to the beta amyloid (Aβ ) pathology can be traced only in sAD animal model, rats treated intracerebroventricularly with streptozotocin (STZ-icv). STZ enters the cell through glucose transporter type 2 (GLUT2) and selectively damages insulin producing/secreting cells and IR, as well as GLUT2. The time course of brain insulin system dysfunction following damage induced by icv application of GLUT2- and IR-toxic drug was investigated in this sAD model. Methods: Male Wistar rats (3-4 month old, 6-8 per group) were treated bilaterally icv with STZ (1-3 mg/kg) and followed after 1, 3 and 6 months for the memory (Morris Water Maze Swimming Test), hippocampal neurochemistry (RT-PCR for insulin-1 /Ins-1/, IR and insulin degrading enzyme /IDE/, immunoblotting for IR, protein kinase B /Akt/PKB/, glycogen synthase kinase 3 /GSK-3/, IDE, tau protein, and Elisa assay for tyrosine kinase /TK/), and histology (immunohistochemistry and Congo red staining for Aβ ). Data were analysed by Kruskal Wallis median and Mann Whitney U test. Results: One month following the STZ-icv treatment IR mRNA and protein were decreased (p<0.05). Three months following the STZ-icv treatment Ins-1 and IR mRNA were decreased (p<0.05) and IR-TK activity increased (p<0.05). This was followed by alterations (p<0.05) of downstream IR signaling elements, decreased expression of Akt/PKB and p-GSK-3/GSK-3 ratio, increased expression of hyperphosphorylated tau protein, and decreased expression of IDE mRNA and protein. Aβ -like congophilic capillary aggregates (cerebral amyloid angiopathy) and Aβ 1-42 intraneuronal aggregates were found after 3 months. Decreased expression of Ins-1, IR and IDE mRNA, IR and IDE protein were found 6 months after STZicv treatment when Aβ 1-42 primitive plaques were found in hippocampal/cortical regions. Cognitive deficits were found at each time point. Conclusions: STZ-icv induced damage of brain GLUT2 and IR leads to insulin resistant brain state eventually triggering Aβ pathology in animal sAD model. Supported by DAAD and MZOS.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti
POVEZANOST RADA
Projekti:
108-1080003-0020 - Mozak, eksperimentalni i cerebralni dijabetes i kognitivni i drugi poremećaji (Šalković-Petrišić, Melita, MZOS ) ( CroRIS)
Ustanove:
Medicinski fakultet, Zagreb
