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

Autori
Osmanović-Barilar, Jelena ; Knezović, Ana ; Grünblatt, Edna ; Riederer, Peter ; Šalković- Petrišić, Melita

Izvornik
Journal of neural transmission (0300-9564) 122 (2015), 4; 565-576

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Insulin signalling ; brain ; streptozotocin ; IDE ; tau ; Alzheimer

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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