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

Znanstveni rad - Izvorni znanstveni rad

• Autor: Jelena Osmanović Barilar
• Autor: Ana Knezović
• Autor: Edna Grünblatt
• Autor: Peter Riederer
• Autor: Melita Šalković-Petrišić
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti

Sažetak (engleski)

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.

• Ključne riječi (engleski): 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
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Završna verzija rukopisa prihvaćena za objavljivanje (postprint)
• Naslov časopisa: Journal of Neural Transmission
• Brojčani podaci: vol. 122, br. 4, str. 565-576
• p-ISSN: 0300-9564
• DOI: https://doi.org/10.1007/s00702-014-1323-y
• URN:NBN: urn:nbn:hr:105:181257
• Datum objave publikacije: 2015-04
• URL dokumenta: https://doi.org/10.1007/s00702-014-1323-y
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-28 08:33:32