Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction

Grünblatt, Edna and Bartl, Jasmin and Iuhos, Diana-Iulia and Knezović, Ana and Trkulja, Vladimir and Riederer, Peter and Walitza, Susanne and Šalković-Petrišić, Melita (2015) Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction. Journal of Molecular Psychiatry, 3 (1). p. 6. ISSN 2049-9256

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BACKGROUND The spontaneously hypertensive rat (SHR) has been used to model changes in the central nervous system associated with cognitive-related disorders. Recent human and animal studies indicate a possible relationship between cognitive deficits, insulin resistance and hypertension. We aimed to investigate whether cognitively impaired SHRs develop central and/or peripheral insulin resistance and how their cognitive performance is influenced by the animal's sex and age as well as strains used for comparison (Wistar and Wistar-Kyoto/WKY). ----- METHODS Three and seven-month-old SHR, Wistar, and WKY rats were studied for their cognitive performance using Morris Water Maze (MWM) and Passive Avoidance tests (PAT). Plasma glucose and insulin were obtained after oral glucose tolerance tests. Cerebral cortex, hippocampus, and striatum status of insulin-receptor (IR) β-subunit and glycogen synthase kinase-3β (GSK3β) and their phosphorylated forms were obtained via ELISA. ----- RESULTS SHRs performed poorly in MWM and PAT in comparison to both control strains but more pronouncedly compared to WKY. Females performed poorer than males and 7-month-old SHRs had poorer MWM performance than 3-month-old ones. Although plasma glucose levels remained unchanged, plasma insulin levels were significantly increased in the glucose tolerance test in 7-month-old SHRs. SHRs demonstrated reduced expression and increased activity of IRβ-subunit in cerebral cortex, hippocampus, and striatum with different regional changes in phospho/total GSK3β ratio, as compared to WKYs. ----- CONCLUSION Results indicate that cognitive deficits in SHRs are accompanied by both central and peripheral insulin dysfunction, thus allowing for the speculation that SHRs might additionally be considered as a model of insulin resistance-induced type of dementia.

Item Type: Article
Additional Information: © Grünblatt et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​4.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0​) applies to the data made available in this article, unless otherwise stated.
Departments: Katedra za farmakologiju
Depositing User: Marijan Šember
Status: Published
Grünblatt, EdnaUNSPECIFIED
Iuhos, Diana-IuliaUNSPECIFIED
Trkulja, VladimirUNSPECIFIED
Riederer, PeterUNSPECIFIED
Walitza, SusanneUNSPECIFIED
Šalković-Petrišić, MelitaUNSPECIFIED
Date: 4 June 2015
Date Deposited: 02 Feb 2016 13:13
Last Modified: 23 Jul 2020 06:48
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