Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease

Osmanović Barilar, Jelena and Knezović, Ana and Grünblatt, Edna and Riederer, Peter and Šalković-Petrišić, Melita (2015) Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease. Journal of Neural Transmission, 122 (4). pp. 565-576. ISSN 0300-9564

[img] PDF - Accepted Version
Download (2MB)


Sporadic Alzheimer disease (sAD) is associated with impairment of insulin receptor (IR) signalling in the brain. Rats used to model sAD develop insulin-resistant brain state following intracerebroventricular treatment with a betacytotoxic drug streptozotocin (STZ-icv). Brain IR signalling has been explored usually at only one time point in periods ≤3 months after the STZ-icv administration. We have investigated insulin signalling in the rat hippocampus at five time points in periods ≤9 months after STZ-icv treatment. Male Wistar rats were given vehicle (control)- or STZ (3 mg/kg)-icv injection and killed 0.5, 1, 3, 6 and 9 months afterwards. Insulin-1 (Ins-1), IR, phospho- and total (p/t)-glycogen synthase kinase 3-β (GSK-3β), p/t-tau and insulin degrading enzyme (IDE) mRNA and/or protein were measured. Acute upregulation of tau and IR mRNA (p < 0.05) was followed by a pronounced downregulation of Ins-1, IR and IDE mRNA (p < 0.05) in the course of time. Acute decrement in p/t-tau and p/t-GSK-3β ratios (p < 0.05) was followed by increment in both ratios (3-6 months, p < 0.05) after which p/t-tau ratio demonstrated a steep rise and p/t-GSK-3β ratio a steep fall up to 9 months (p < 0.05). Acute decline in IDE and IR expression (p < 0.05) was followed by a slow progression of the former and a slow recovery of the latter in 3-9 months. Results indicate a biphasic pattern in time dependency of onset and progression of changes in brain insulin signalling of STZ-icv model (partly reversible acute toxicity and chronic AD-like changes) which should be considered when using this model as a tool in translational sAD research.

Item Type: Article
MeSH: Alzheimer Disease/metabolism ; Animals ; Disease Models, Animal ; Disease Progression ; Follow-Up Studies ; Glycogen Synthase Kinase 3/metabolism ; Hippocampus/metabolism ; Insulysin/metabolism ; Male ; Phosphorylation ; RNA, Messenger/metabolism ; Random Allocation ; Rats, Wistar ; Receptor, Insulin/metabolism ; Signal Transduction ; Streptozocin ; Time Factors ; tau Proteins/metabolism
Departments: Katedra za farmakologiju
Depositing User: Marijan Šember
Status: Published
Osmanović Barilar, JelenaUNSPECIFIED
Grünblatt, EdnaUNSPECIFIED
Riederer, PeterUNSPECIFIED
Šalković-Petrišić, MelitaUNSPECIFIED
Date: April 2015
Date Deposited: 07 Mar 2016 10:51
Last Modified: 23 Jul 2020 08:41
Subjects: /
Related URLs:

Actions (login required)

View Item View Item


Downloads per month over past year