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


Grünblatt, Edna; Bartl, Jasmin; Iuhos, Diana-Iulia; Knezovic, Ana; Trkulja, Vladimir; Riederer, Peter; Walitza, Susanne; Salkovic-Petrisic, Melita (2015). Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction. Journal of Molecular Psychiatry, 3(6):online.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
04 Faculty of Medicine > Neuroscience Center Zurich
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:17 Jul 2015 09:16
Last Modified:13 Jun 2016 21:32
Publisher:BioMed Central
ISSN:2049-9256
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s40303-015-0012-6
PubMed ID:26110057

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