title: Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Clinics of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032 Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland ; University Hospital, Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Würzburg, Füchsleinstr. 15, D-97080 Würzburg, Germany ; University Clinics of Child and Adolescent Psychiatry, University of Zurich, Wagistrasse 12, CH-8952 Schlieren, Switzerland.
authors.forename: Edna
authors.initials: E
authors.lastname: Grünblatt
authors.affiliation: University Clinics of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032 Zurich, Switzerland.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bartl
authors.affiliation: University Hospital, Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Würzburg, Füchsleinstr. 15, D-97080 Würzburg, Germany.
authors.forename: Diana-Iulia
authors.initials: DI
authors.lastname: Iuhos
authors.affiliation: Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 11, 10 000 Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Knezovic
authors.affiliation: Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 11, 10 000 Zagreb, Croatia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trkulja
authors.affiliation: University Hospital, Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Würzburg, Füchsleinstr. 15, D-97080 Würzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.affiliation: University Clinics of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032 Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
authors.affiliation: Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 11, 10 000 Zagreb, Croatia.
authors.forename: Melita
authors.initials: M
authors.lastname: Salkovic-Petrisic
keywords: Age; Control strain; Gender; Glycogen synthase-kinase 3β; Insulin resistance; Learning and memory; Spontaneously hypertensive rat