@article{GruenblattBartlIuhosetal.2015,
  author    = {Gr{\"u}nblatt, Edna and Bartl, Jasmin and Iuhos, Diana-Iulia and Knezovic, Ana and Trkulja, Vladimir and Riederer, Peter and Walitza, Susanne and Salkovic-Petrisic, Melita},
  title     = {Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction},
  series = {Journal of Molecular Psychiatry},
  volume    = {3},
  journal   = {Journal of Molecular Psychiatry},
  number    = {6},
  doi       = {10.1186/s40303-015-0012-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149593},
  year      = {2015},
  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.},
  language  = {en}
}
@article{BartlScholzHinterbergeretal.2011,
  author    = {Bartl, Jasmin and Scholz, Claus-J{\"u}rgen and Hinterberger, Margareta and Jungwirth, Susanne and Wichart, Ildiko and Rainer, Michael K. and Kneitz, Susanne and Danielczyk, Walter and Tragl, Karl H. and Fischer, Peter and Riederer, Peter and Gr{\"u}nblatt, Edna},
  title     = {Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzymegene},
  series = {BMC Medical Genetics},
  volume    = {12},
  journal   = {BMC Medical Genetics},
  number    = {151},
  doi       = {10.1186/1471-2350-12-15},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137744},
  year      = {2011},
  abstract  = {Background Insulin-degrading enzyme (IDE) is the ubiquitously expressed enzyme responsible for insulin and amyloid beta (Aβ) degradation. IDE gene is located on chromosome region 10q23-q25 and exhibits a well-replicated peak of linkage with Type 2 diabetes mellitus (T2DM). Several genetic association studies examined IDE gene as a susceptibility gene for Alzheimer's disease (AD), however with controversial results. Methods We examined associations of three IDE polymorphisms (IDE2, rs4646953; IDE7, rs2251101 and IDE9, rs1887922) with AD, Aβ42 plasma level and T2DM risk in the longitudinal Vienna Transdanube Aging (VITA) study cohort. Results The upstream polymorphism IDE2 was found to influence AD risk and to trigger the Aβ42 plasma level, whereas the downstream polymorphism IDE7 modified the T2DM risk; no associations were found for the intronic variant IDE9. Conclusions Based on our SNP and haplotype results, we delineate the model that IDE promoter and 3' untranslated region/downstream variation may have different effects on IDE expression, presumably a relevant endophenotype with disorder-specific effects on AD and T2DM susceptibility.},
  language  = {en}
}