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Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease.
J Neural Transm (Vienna). 2015 Apr; 122(4):565-76.JN

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 11, HR 10000, Zagreb, Croatia, josmanov@mef.hr.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25503661

Citation

Barilar, J Osmanovic, et al. "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 (Vienna, Austria : 1996), vol. 122, no. 4, 2015, pp. 565-76.
Barilar JO, Knezovic A, Grünblatt E, et al. Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease. J Neural Transm (Vienna). 2015;122(4):565-76.
Barilar, J. O., Knezovic, A., Grünblatt, E., Riederer, P., & Salkovic-Petrisic, M. (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 (Vienna, Austria : 1996), 122(4), 565-76. https://doi.org/10.1007/s00702-014-1323-y
Barilar JO, et al. Nine-month Follow-up of the Insulin Receptor Signalling Cascade in the Brain of Streptozotocin Rat Model of Sporadic Alzheimer's Disease. J Neural Transm (Vienna). 2015;122(4):565-76. PubMed PMID: 25503661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease. AU - Barilar,J Osmanovic, AU - Knezovic,A, AU - Grünblatt,E, AU - Riederer,P, AU - Salkovic-Petrisic,M, Y1 - 2014/12/12/ PY - 2014/07/28/received PY - 2014/10/01/accepted PY - 2014/12/16/entrez PY - 2014/12/17/pubmed PY - 2015/12/19/medline SP - 565 EP - 76 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 122 IS - 4 N2 - 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. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/25503661/Nine_month_follow_up_of_the_insulin_receptor_signalling_cascade_in_the_brain_of_streptozotocin_rat_model_of_sporadic_Alzheimer's_disease_ L2 - https://doi.org/10.1007/s00702-014-1323-y DB - PRIME DP - Unbound Medicine ER -